Ndị ọkà mmụta sayensị jikọtara ogologo telomere na ọrịa shuga

Micrograph nke chromosomes mmadụ na telomeres (egosiri na pink). (Foto: Mary Armanios)

Telomeres na-emeghachi usoro nke DNA na-echebe nsọtụ chromosom. Ka ahụ ha na-emewanye agadi, ha na-adịkarị mkpụmkpụ. N'okwu a, mkpụrụ ndụ ana - ewepụ ike ha ikari n'ụzọ ọ bụla, ma n'ikpeazụ, na - anwụ. Ngwakọta nke Telomere dị mkpirikpi na ọrịa kansa, ọrịa ngụ, na ọrịa ndị ọzọ metụtara afọ. Ọrịa shuga, metụtarakwa ịka nká, na-emetụta otu onye n’ime ndị okenye anọ karịrị afọ 60.

Nchoputa nke ndi sayensi na Mahadum Johns Hopkins, nke ebiputara na akwukwo a bu PLoS One, dabere na nlere anya nke Mary Armanios, onye dọrọ uche gaa n’iru nke nnwekọrịta mmekọrịta dị n’etiti ọrịa shuga na ọrịa ọnyụnyụ ọbara (ọrịa dyskeratosis), ọrịa ọrịa na - adịghị ahụkebe nke mmebi nke usoro mmezi ahụ. telomere ogologo. N'ime ndị ọrịa nwere dyskeratosis e ketara eketa, a na-ahụkarị isi awọ na ọdịda mbụ nke ọtụtụ akụkụ ahụ.

Disgenra diskeratosis bụ ọrịa na - ebute ndị mmadụ na nká. Anyị maara na ọrịa shuga mụbara na afọ, n'ihi ya anyị tụrụ aro na enwere ike ịnwekwa njikọ n'etiti telomeres na ọrịa shuga, "Armanios, onye otu prọfesọ na oncology na Kimmel Cancer Center, Mahadum Johns Hopkins kwuru.

N'ime ndị ọrịa nwere ọrịa shuga, emepụtaghị insulin zuru ezu, sel ha enweghị ike iji ya rụọ ọrụ nke ọma, nke na-eduga mmebi nke usoro shuga dị n'ọbara.

Armanios mụụrụ ụmụ irighiri ihe dị na telomeres dị mkpụmkpụ na mkpụrụ ndụ beta na-emepụta insulin. Ọ chọpụtara na n'agbanyeghị ọnụnọ ọnụọgụ beta dị mma na-achọ mma, ọkwa shuga dị n'ọbara ndị a dị elu, mkpụrụ ndụ ndị ahụ na-enyocha insulin abụọ dị ala karịa nke anụmanụ nke ìgwè na-ahụ maka ya.

Armanios kọwara, "Nke a kwekọrọ na mmalite nke ọrịa shuga na mmadụ, mgbe mkpụrụ ndụ nwere nsogbu izochi insulin iji zoo shuga,” Armanios kọwara. “N'ọtụtụ ndị dị otú ahụ n'ọtụtụ ọnọdụ nzuzo insulinArmanios kwuru, sị, "Site na nrụpụta ike site na mitochondria ruo na akara ngosi nke calcium, mkpụrụ ndụ na-arụ ọrụ ọkara nke otu ha kwesịrị,"

Na mkpụrụ ndụ beta nke ụmụ oke nwere telomeres dị mkpụmkpụ, ndị ọkà mmụta sayensị achọpụtala ngbanwe nke usoro p16 nke metụtara ịka nká na ọrịa shuga. Na mgbakwunye, ọtụtụ mkpụrụ ndụ ihe nketa nke dị mkpa maka nzuzo insulin, gụnyere ụzọ nke na-achịkwa akara kalisiki, ka gbanwere n’ime ha. N'ime ndị na-ahụ maka njikwa, ọchọghị ụdị njehie a.

Studiesfọdụ nnyocha emere n'oge gara aga gosiri na ndị ọrịa nwere ọrịa shuga nwere obere telomeres, mana ọ na-abawanye ọrịa shuga n'ihe ize ndụ ma ọ bụ nsonaazụ nke ọrịa a, edobeghị anya.

Ka nká bụ ihe kasị akpata ọrịa shuga. Na mgbakwunye, nketa ezinụlọ na-arụ ọrụ dị oke mkpa. Ogologo telomeres bụ ihe e ketara eketa ma nwee ike ime ka ndị mmadụ na-enwekarị ọrịa shuga, ”Armanios kwenyere.

Dabere na ọrụ a, Armanios kwubiri na ogologo telomere nwere ike ịrụ ọrụ dị ka mmepe nke mmepe oria shuga. N'ime nyocha ọzọ, ndị ọkà mmụta sayensị na-eme atụmatụ ịchọpụta ma ọ ga-ekwe omume ịkọ ihe ga - eme ka ọrịa a dabere na telomere ogologo. ”

Kedu ka telomeres na mbufụt dị mkpụmkpụ si akpata ọrịa shuga

Kedu ihe kpatara ndị nwere oke abụba ji eme ka insulin na-eguzogide ọgwụ na ohere ha nwere ịrịa ọrịa shuga? Oriri na-ezighi ezi, ndụ ịla n’iyi na nchekasị so mee ka e nwee abụba afọ na mmụba n’ọbara shuga. N'ime ndị nwere afọ, telomeres na-adị mkpụmkpụ karịa afọ <5>, o nwekwara ike ịbụ na mbelata ha na-eme ka nsogbu ahụ na-egbochi insulin na-egbochi nsogbu ahụ. N'ime ọmụmụ Danish nke ụmụ ejima 338 sonyere na ya, achọpụtara na telomeres dị mkpụmkpụ na-emebi ihe na-egbochi insulin n'afọ na-esote afọ 12. N'ime ụmụ ejima abụọ, otu n'ime ndị tololores dị mkpụmkpụ gosipụtara ogo ukwuu nke nguzogide insulin <6>.

Ndị ọkà mmụta sayensị egosipụtala mkpakọrịta ugboro ugboro na telomeres dị mkpirikpi na ọrịa shuga. Telomere dị mkpụmkpụ na-abawanye ohere nke ibute ọrịa shuga: ndị nwere ọrịa telomere dị mkpụmkpụ mkpụmkpụ mmadụ yikarịrị ka ga-enweta ọrịa a karịa ndị ọzọ. Ọrịa shuga na-amalite n’oge wee na-eto n’ike n’ike. Nnyocha nke ndị India, bụ ndị n’ihi ọtụtụ ihe nọ n’ihe ize ndụ ka ukwuu maka ọrịa shuga, na-arụpụtakwa ihe na-akụda mmụọ. N’India nke nwere telomeres dị mkpụmkpụ, o yikarịrị ka ọ ga-ebute ọrịa shuga n’afọ ise na-abịanụ karịa nke ndị nnọchi anya otu agbụrụ nwere ogologo telomeres <7>. Nyochaa meta nke ọmụmụ metụtara ihe karịrị mmadụ 7,000 gosipụtara na telomeres dị mkpụmkpụ na mkpụrụ ndụ ọbara bụ ihe ama ama a pụrụ ịdabere na ya nke ọrịa shuga <8> n'ọdịnihu.

Ọ bụghị naanị na anyị maara usoro mmepe nke ọrịa shuga, kama anyị nwere ike lebanye anya na pancreas ma hụ ihe na-eme na ya. Mary Armanios na ndị ọrụ ibe gosipụtara na ụmụ oke, mgbe a na-ebelata telomeres n'ime ahụ (ndị sayensị gosipụtara nke a site na mkpụrụ ndụ ihe ọmụmụ), mkpụrụ ndụ beta nke palọ na-efunyụọ ikike imepụta insulin <9>. Mkpụrụ ndụ na-adị na pancreas na-aka nká, telomere ha na-adị mkpụmkpụ, ha enweghịzi ike idegharị ahazi mkpụrụ ndụ beta nke na-ahụ maka imepụta insulin na nhazi nke ọkwa ya. Mkpụrụ ndụ ndị a na-anwụ. Typedị ọrịa shuga m na-agbadata azụmaahịa. Site n'ọrịa shuga II nkịtị, mkpụrụ ndụ beta anaghị anwụ anwụ, mana arụmọrụ ya anaghị arụ ọrụ. N'ihi ya, na nke a, oke, telomeres dị mkpirikpi nwere ike ịrụ ọrụ.

N’ime onye ọzọ nwere ahụ ike, enyi anyị ochie nwere ike idobere akwa site na abụba afọ na ọrịa shuga - ọnya na-adịghị ala ala. Abụba abba na-enye aka na mmepe nke mbufụt karịa, sịnụ, abụba n'úkwù. Mkpụrụ ndụ na-ewepụtakarị ihe na-akpata pro-mkpali nke na - emebi mkpụrụ ndụ nke ihe ahụ ji alụso ọrịa ọgụ, na - eme ka ha bụrụ mbelata ma na - emebi telomeres ha. Dịka icheta, a na-anabata mkpụrụ ndụ ochie, n’aka nke ya, iji zipu akara na-akwụsịghị akwụsị nke na-akpali mbufụt n’ime ahụ niile - a na-enweta okirikiri ọjọọ.

Ọ bụrụ na ị nwere oke abụba, ị ga-akpachara anya iji chebe onwe gị pụọ na mbufụt na-adịghị ala ala, telomeres dị mkpirikpi, na ọrịa metabolic. Mana tupu ịmalite iri nri iji kpochapụ abụba afọ, gụọ isiakwụkwọ a ruo na njedebe: ịnwere ike ikpebi na nri ga-aka njọ. Echegbula: anyị ga-enye gị ụzọ ndị ọzọ iji mezie metabolism gị.

Ibepu akwukwo banyere sayensi banyere ogwu na nlekọta ahuike, onye dere akwukwo banyere sayensi - Brailova Nataliya Vasilievna, Dudinskaya Ekaterina Nailevna, Tkacheva Olga Nikolaevna, Shestakova Marina Vladimirovna, Strazhesko Irina Dmitrievna, Akasheva Dariga Uaydinichna Vilklọvanna, Vloklava, Vloklava, Shea Anatolyevich

Ebumnuche nke ọmụmụ a bụ ịmụ mmekọrịta nke mbufụt na-adịghị ala ala, nrụgide oxidative, na usoro ọmụmụ telomere n'ime ndị nwere ụdị ọrịa shuga 2 (T2DM). Ihe na usoro. Ọmụmụ ihe ahụ gụnyere ndị ọrịa 50 nwere ụdị ọrịa shuga 2 na-enweghị ihe ngosipụta ọgwụgwọ na-arịa ọrịa obi (CVD) na ndị 139 nọ na ndị na-ahụ maka njikwa. A na-enyocha ọnọdụ nke metabolism metabolism, ogo nke nrụgide oxidative (MDA malondialdehyde) na mbufụt na-adịghị ala ala (fibrinogen, C-reactive CRP protein, interleukin-6 IL-6), na-atụle ogologo nke lymphocytic telomeres na telomerase ọrụ. Nsonaazụ N'ime ndị ọrịa nwere ụdị ọrịa shuga 2, telomere ogologo dị mkpụmkpụ (p = 0.031), ọrụ telomerase dị ala (p = 0.039), ogo nke mbufụt (ọkwa CRP na fibrinogen) dị elu karịa na otu nchịkwa. Ejiri telomere ogologo kesaa ndị ọrịa niile. N'ime ndị ọrịa nwere T2DM, CRP na ọkwa fibrinogen dị elu na ndị mmadụ nwere obere telomeres (p = 0.02). Mgbe ị na-atụnyere otu dị iche iche na telomere “ogologo”, enweghị ọdịiche dị na ọkwa CRP (p = 0.93). N'ime ndị ọrịa nwere ọrịa shuga nke 2 na nke telomerase dị ala, ogo nke mbufụt na-adịghị ala ala kasịnụ. N'ime ndị ọrịa nwere ụdị shuga 2, a hụrụ mmekọrịta n'etiti telomere ogologo na ọkwa CRP (r = -0.40, p = 0.004). Mmechi Ọrịa na-egbu oge na ịka nká na ndị ọrịa nwere ụdị shuga 2 na-ekwuputa karịa na nchịkwa. Agbanyeghị, n'ime ndị ọrịa nwere telomere “ogologo oge”, ihe ịrịba ama nke mbufụt na-adịghị ala ala adịghị iche na nke ndị ahụ siri ike. Ikekwe telomeres dị ogologo “na-echebe ndị ọrịa nwere T2DM pụọ na mmetụta mmebi nke ọnya na-adịghị ala ala.

Telomere ogologo, ọrụ telomerase na usoro na-agbanwe na ndị ọrịa nwere ụdị ọrịa mellitus 2 dị

Ebumnuche. Iji mụọ mkpakọrịta nke ọrịa na-adịghị ala ala, nrụgide oxidative na telomere bayoloji na ndị nwere ọrịa shuga 2 bụ ọrịa mellitus (T2DM). Ihe na .zọ. Ngụkọta ndị ọrịa 50 nwere T2D na ndị na-enweghị ọrịa obi (CVD) na ndị 139 sitere na ndị na-achịkwa esonye n'ọmụmụ ihe ahụ. A tụlere isiokwu niile maka metabolism metabolism, nrụgide oxidative (malondialdehyde (MDA)), mbufụt (C-reactive protein CRP, fibrinogen, interleukin-6), lymphocyte telomere ogologo, ọrụ telomerase. Nsonaazụ N'ime ndị ọrịa mamịrị ọrịa telomeres dị mkpụmkpụ karịa na njikwa (9.59 ± 0.54 na 9.76 ± 0.47, p = 0.031), ọrụ telomerase dị ala (0.47 ± 0.40 na 0.62 ± 0.36, p = 0.039), mbufụt (CRP, fibrinogen dị elu) dị elu. . Ndị ọrịa niile bụ ogologo> telomere ogologo. Na T2DM otu CRP dị elu na ndị ọrịa nwere telomeres “dị mkpụmkpụ” (7.39 ± 1.47 na 3.59 ± 0.58 mg / L, p = 0.02). Enweghị ọdịiche dị mkpa na ọkwa nke mbufụt na-adịghị ala ala na nrụgide oxidative na telomeres 'ogologo' CRP 3.59 ± 0.58 na 3.66 ± 0.50 mg / L (p = 0.93), MDA 2.81 ± 0.78 na 3.24 ± 0.78 mmol / l ( p = 0.08). Ndị ọrịa mamịrị na-arịa ọrịa telomeres “mkpụmkpụ” nwere nnukwu mbufụt: CRP 7.39 ± 1.47 na 4.03 ± 0.62 mg / L (p = 0.046), mụbara fibrinogen, 0.371 na 0.159 (p = 0.022). Ndị ọrịa niile bụ ọrụ telomerase. Ọnọdụ mgbu na-adịghị ala ala kachasị ukwuu na T2DM yana ọrụ "dị ala" nke telomerase. Enwere mmekọrịta n'etiti telomere ogologo na CRP na ndị ọrịa T2DM (r = -0.40, p = 0.004). Mmechi. Ọrịa ọgbụgba na ịka mkpụrụ ndụ ka ekwuputara na ndị ọrịa nwere T2DM. Agbanyeghị, n'agbanyeghị ọrịa shuga, ihe ịrịba ama nke mbufụt na-adịghị ala ala dị ntakịrị na ndị ọrịa nwere telomere “ogologo” ma e jiri ya tụnyere ndị nwere ahụike. Ikekwe ogologo telomeres na-echebe ndị ọrịa mamịrị pụọ na ihe ọjọọ nke mbufụt na-adịghị ala ala.

Ederede nke ọrụ sayensị na isiokwu "ogologo Telomere, telomerase ọrụ, na usoro mgbanwe ha na onye ọrịa nwere ụdị shuga 2"

Telomere ogologo, ọrụ telomerase na usoro nke mgbanwe ha na onye ọrịa nwere ọrịa shuga nke 2

Ph.D. N.V. BRAYLOVA1 *, Ph.D. E.N. DUDINSKAYA1, MD O.N. TKACHEVA1, onye otu kwekọrọ RAS M.V. SHESTAKOVA2, Ph.D. I.D. STRAZHESKO1, nwa akwukwo nke sayensị D.U. AKASHEV1, E.V. PLOKHOVA1, V.S. Pykhtina1, V.A. VYGODIN1, prof. S.A. FIGHTERS1

1 FSBI “Researchlọ Ọrụ Nnyocha Ọchịchị Maka Ọgwụ Mgbochi”, Moscow, Russia, 2 FSBI “Endocrinological Research Center” nke Ministri Ahụike Russia, Moscow, Russia.

Ebumnuche nke ọmụmụ a bụ ịmụ mmekọrịta nke mbufụt na-adịghị ala ala, nrụgide oxidative, na usoro ọmụmụ telomere n'ime ndị nwere ụdị ọrịa shuga 2 (T2DM).

Ihe na usoro. Ọmụmụ ihe ahụ gụnyere ndị ọrịa 50 nwere ụdị ọrịa shuga 2 na-enweghị ihe ngosipụta ọgwụgwọ na-arịa ọrịa obi (CVD) na ndị 139 nọ na ndị na-ahụ maka njikwa. A na-enyocha steeti carbohydrate metabolism, ogo nke nrụgide oxidative (malondialdehyde - MDA) na mbufụt na-adịghị ala ala (fibrinogen, C-reactive protein - CRP, interleukin-6 - IL-6), na-atụle ogologo nke lymphocyte telomeres na telomerase ọrụ.

Nsonaazụ N'ime ndị ọrịa nwere ụdị ọrịa shuga 2, telomere ogologo dị mkpụmkpụ (p = 0.031), ọrụ telomerase dị ala (p = 0.039), ogo nke mbufụt (ọkwa CRP na fibrinogen) dị elu karịa na otu nchịkwa. Ejiri telomere ogologo kesaa ndị ọrịa niile. N'ime ndị ọrịa nwere T2DM, CRP na ọkwa fibrinogen dị elu na ndị mmadụ nwere obere telomeres (p = 0.02). Mgbe ị na-atụnyere otu dị iche iche na telomere “ogologo”, enweghị ọdịiche dị na ọkwa CRP (p = 0.93). N'ime ndị ọrịa nwere ọrịa shuga nke 2 na nke telomerase dị ala, ogo nke mbufụt na-adịghị ala ala kasịnụ. N'ime ndị ọrịa nwere ụdị shuga 2, a hụrụ mmekọrịta n'etiti telomere ogologo na ọkwa CRP (r = -0.40, p = 0.004).

Mmechi Ọrịa na-egbu oge na ịka nká na ndị ọrịa nwere ụdị shuga 2 na-ekwuputa karịa na nchịkwa. Agbanyeghị, n'ime ndị ọrịa nwere telomere “ogologo oge”, ihe ịrịba ama nke mbufụt na-adịghị ala ala adịghị iche na nke ndị ahụ siri ike. Ikekwe telomeres dị ogologo “na-echebe ndị ọrịa nwere T2DM pụọ na mmetụta mmebi nke ọnya na-adịghị ala ala.

Okwu dị mkpirikpi: telomere ogologo, ọrụ telomerase, ọrịa shuga mellitus, mbufụt na-adịghị ala ala, nrụgide oxidative.

Telomere ogologo, ọrụ telomerase na usoro na-agbanwe na ndị ọrịa nwere ụdị ọrịa mellitus 2 dị

N.V. BRAILOVA1, E.N. DUDINSKAYA1, O.N. TKACHEVA1, M.V. SHESTAKOVA2, I.D. STRAZHESKO1, D.U. AKASHEVA1, E.V. PLOCHOVA1, V.S. PYKHTINA1, V.A. VYGODIN1, S.A. BOYTSOV1

'Researchlọ Ọrụ Nnyocha Ọchịchị Maka Ọgwụ Mgbochi Ọgwụ, Moscow, Russia, 2 Nnyocha Nnyocha Endocrinology, Moscow, Russia

Ebumnuche. Iji mụọ mkpakọrịta nke ọrịa na-adịghị ala ala, nrụgide oxidative na telomere bayoloji na ndị nwere ọrịa shuga 2 bụ ọrịa mellitus (T2DM).

Ihe na .zọ. Ngụkọta ndị ọrịa 50 nwere T2D na ndị na-enweghị ọrịa obi (CVD) na ndị 139 sitere na ndị na-achịkwa esonye n'ọmụmụ ihe ahụ. A tụtara ntụ ọka niile maka metabolism metabolism, otu oxelomeres: CRP 3.59 ± 0.58 na 3.66 ± 0.50 mg / L (p = 0.93), MDA 2.81 ± 0.78 na 3.24 ± 0.78 mmol / l (p = 0.08). Ndị ọrịa mamịrị na-arịa ọrịa telomeres “mkpụmkpụ” nwere nnukwu mbufụt: CRP 7.39 ± 1.47 na 4.03 ± 0.62 mg / L (p = 0.046), mụbara fibrinogen, 0.371 na 0.159 (p = 0.022). Ndị ọrịa niile bụ div>

Mmechi. Ọrịa ọgbụgba na ịka mkpụrụ ndụ ka ekwuputara na ndị ọrịa nwere T2DM. Agbanyeghị, n'agbanyeghị ọrịa shuga, ihe ịrịba ama nke mbufụt na-adịghị ala ala dị ntakịrị na ndị ọrịa nwere telomere “ogologo” ma e jiri ya tụnyere ndị nwere ahụike. Ikekwe ogologo telomeres na-echebe ndị ọrịa mamịrị pụọ na ihe ọjọọ nke mbufụt na-adịghị ala ala.

Isi okwu: ogologo telomere, ọrụ telomerase, ọrịa shuga, ọrịa obi na-adịghị ala ala, nrụgide oxidative.

Ahụhụ Oxidative na mbufụt na-adịghị ala ala dịka ihe ndabere maka ịka nká nke ndu

Ọrịa shuga mellitus (DM) na-esokwa mgbanwe ọsọ ọsọ na akwara ọbara, nke na-eme ya bụrụ ihe kacha ebute ọrịa obi (CVD) na ọnwụ. Njikọ data dị mkpa

mgbanwe - hyperglycemia, nguzogide insulin, mkpo nke ngwaahịa njedebe nke glycation (CNG). Hyperinsulinemia na hyperglycemia, yana ịka nká, na-eme ka usoro nke mbufụt na-adịghị ala ala na nrụgide oxidative. N'ime ahụ agadi, dị ka

ọkwa dị ala nke onye ọrịa na-arịa ọrịa shuga, ọkwa nke akara dị iche iche nke mbufụt na-abawanye protein C-reactive (CRP), IL-18, TNF-a (“na-akpasu iwe”), na-abawanye ọrụ nke lipid peroxidation site na nguzobe nke malondialdehyde (MDA) na ụdị oxygen na-arụ ọrụ (ROS) . Ihe ndị a niile na - eduga na njikọta protein na - arụ ọrụ, apoptosis cell yana mmepe nke usoro na - emebi emebi.

Ọmụmụ ihe ọmụmụ nke telomeres na ndị nwere ọrịa shuga nke 2

Otu n'ime ihe kpatara ọnọdụ dị iche iche nke ọrịa vaskụla ụbara na ndị ọrịa nwere ọrịa shuga dị 2 ji bido “ichebe mkpụrụ ndụ ihe nketa” na mbụ site na ikpughe ihe ndị dị na mpụga. Ogologo telomere na ihe omume telomerase nwere ike ikwu na ọrụ nke mkpụrụ ndụ ihe nrịbama nke afọ ndụ nke akwara ọbara. Telomeres bụ akụkụ akụkụ nke mkpụrụ ndụ DNA linear nke na-eji nwayọ nwayọ na nkebi sel ọ bụla. Ozugbo ogologo telomeric DNA ghọrọ ihe dị oke ala, P53 / P21, ụla mkpụrụ ndụ na-akpata, ka a na-eme ka ọ nọgide na-arụ ọrụ metabolic ya. Enwere ihe akaebe na ogologo nke telomeres na leukocytes na-egosipụta ogologo nke telomeres na sel stem ma kwekọọ n'ogologo ha na mkpụrụ ndụ prootito endothelial, nke na-enye anyị ohere ịtụle oke a dị ka akara biomarker nke ọrịa vaskụla agadi. A na - enweta ihe ngosi izizi nke mbelata nke telomere n'ime ndị nwere ọrịa shuga ụdị 2 na ndidi glucose. Ngwakọta nke Telomere dị mkpụmkpụ nwere ike jikọta ya na mmepe nke T2DM, CVD na ịka nká.

Ihe omumu ihe omumu nke abua nke ndu nwere ike ibu telomerase. Telomerase bụ enzyme nke na-agbakwunye usoro DNA ugboro ugboro pụrụ iche na 3'-ọgwụgwụ nke yinye DNA ma na-agụnye telomerase ntụgharị transcriptase (TERT) na telomerase RNA (TERC). N'ime ọtụtụ mkpụrụ ndụ somatic, ọrụ telomerase dị obere. Ọ bụ ezie na telomerase adịghị arụ ọrụ dị mkpa na telomere ogologo homeostasis na agadi, a kwenyere na enzyme a nwere ọrụ ndị na-abụghị telomere dị mkpa iji belata apoptosis, njikwa sel, yana ọrụ mitochondrial na sel mmadụ.

Ọrụ nke mbufụt na-adịghị ala ala na oxidative

nrụgide na mgbanwe na ogologo telomere na ọrụ

telomerase na ndi mmadu nwere oria nke 2

A na - ahụta ihe kachasị akpata usoro pathologies nke metụtara ịka nká na ọkwa cellular dịka nrụgide oxidative na mbufụt na-adịghị ala ala, na-akpata DNA mkpụkọ nke na-adịghị emepụtagharị. Telomere Nnọọ mmetụta

Ha na-ahụ maka mmerụ ahụ na-emebi ihe dị na mkpụrụ ndụ DNA. Na vitro ROS na-ebelata ọdịnaya nke protein nuklia hTERT na mkpụrụ ndụ endothelial na, n'ihi ya, ọrụ telomerase. Telomerase nwere ike ichebe mkpụrụ ndụ ọbara ọcha site na nrụgide oxidative na-enweghị emetụta ogologo oge telomeres. Mmụba na-akpata mmụba na-eme ka mbelata nke abụọ na - eme ka mkpirisi nke mkpụrụ ndụ na n'ihi ntọhapụ nke ROS. Ndalata nke telomeres na-aga n’ihu na mmụba na oge T2DM nwere ike jikọta mbufụt na-adịghị ala ala na nrụgide oxidative. Mmekọrịta dị n'etiti ọrụ telomerase na mbufụt na-adịghị ala ala. Ọrịa na-adịghị ala ala n'oge mmalite site na ụzọ mgbaàmà dị iche iche (gụnyere NF-kB, protein kinase C ma ọ bụ Akt kinase) site na phosphorylation ma ọ bụ transpered nke hTERT nwere ike ime ka telomerase, nke,

Ozi banyere ndị dere:

Brailova Natalia Vasilievna - Ph.D. Dep.nyocha maka ịka nká na igbochi ọrịa ndị metụtara afọ nke Researchlọ Ọrụ Nnyocha Ọchịchị Maka Mgbochi Ọrịa, Moscow, Russia, e-mail: [email protected],

Dudinskaya Ekaterina Nailevna - Nwa akwukwo nke Sciences Medical, Onye nyocha nyocha Dep. Nyocha maka ịka nká na igbochi ọrịa na-akpata ọrịa nke Statelọ Ọrụ Mmefu Ego nke Federal State “Researchlọ Ọrụ Nnyocha Ọchịchị Maka Mgbochi Ọgwụ”, Moscow, Russia,

Tkacheva Olga Nikolaevna - MD, prof., Aka. Dep. na-amụ usoro ịka nká na igbochi ọrịa ọrịa FSBI State Research Center maka Mgbochi Ọrịa, Moscow, Russia, Shestakova Marina Vladimirovna - onye otu kwekọrọ. RAS, Director nke Institute of Diabetes, Vice mgbada Ọrụ sayensị sayensị nke Statelọ Ọrụ Mmefu Ego Steeti Steeti “Endocrinological Scientific Center”, Moscow, Russia, Strazhesko Irina Dmitrievna - onye ndoro anya nke sayensị ọgwụ na ahụike, onye nyocha nyocha dị elu. Dep. Nyocha maka ịka nká na igbochi ọrịa na-akpata ọrịa nke Statelọ Ọrụ Mmefu Ego nke Federal State “Researchlọ Ọrụ Nnyocha Ọchịchị Maka Mgbochi Ọgwụ”, Moscow, Russia,

Akasheva Dariga Uaydinichna - onye nchoputa nke sayensi sayensi, onye nyocha siri ike Dep. Nyocha maka ịka nká na igbochi ọrịa na-akpata ọrịa nke Statelọ Ọrụ Mmefu Ego nke Federal State “Researchlọ Ọrụ Nnyocha Ọchịchị Maka Mgbochi Ọgwụ”, Moscow, Russia,

Plokhova Ekaterina Vladimirovna - nwa akwukwo nke sayensị, ocho oru di elu Dep. Nyocha maka ịka nká na igbochi ọrịa na-akpata ọrịa nke Statelọ Ọrụ Mmefu Ego nke Federal State “Researchlọ Ọrụ Nnyocha Ọchịchị Maka Mgbochi Ọgwụ”, Moscow, Russia,

Pykhtina Valentina Sergeevna - ụlọ nyocha. Dep. Nyocha maka ịka nká na igbochi ọrịa na-akpata ọrịa nke Statelọ Ọrụ Mmefu Ego nke Federal State “Researchlọ Ọrụ Nnyocha Ọchịchị Maka Mgbochi Ọgwụ”, Moscow, Russia,

Vygodin Vladimir Anatolyevich - onye nyocha dị elu ụlọ nyocha. biostatistics Federal State Budgetary Institution “State Research Center for Mgbochi Medicine”, Moscow, Russia, Sergey Anatolyevich Boytsov - MD, prọfesọ, aka. Dep. Cardiology na Molecular Genetics, Onye isi, Researchlọ Ọrụ Nnyocha Ọchịchị Maka Mgbochi Ọrịa, Moscow, Russia

Piano, kwụọ ụgwọ maka ikelata mkpụmkpụ nke ahụ. Agbanyeghị, na ngwụsị nke mbufụt nke na-agwụ ike, ọrụ telomerase na-ebelata, nke na-eduga n'ibelata telomeres.

Ebumnuche nke ọmụmụ a bụ ịmụ mmekọrịta nke mbufụt na-adịghị ala ala na nrụgide oxidative na telomere bayoloji n'ime ndị nwere ọrịa shuga 2.

Ihe na usoro

Otu ihe omumu gosiputara ndi oria nwere oria nke abuo nke nyochara ihe nlere anya na Federal State Budget Scientific Research Center for Surgery na 2012-2013. Ndi otu a nwere ndi oria noo n’agbata iri-ano rue iri-ano na asaa n’enwe oria n’enweghi ihe kariri onwa iri na abuo na ihe HbA1c nwere nke 6.5 ruo 9.0%. Otu njikwa ahụ gụnyere ndị na-enweghị T2DM na-enweghị ngosipụta ọgwụgwọ nke CVD, bụ onye tụgharịrị na etiti maka ndụmọdụ mgbochi.

Usoro iche: ọrịa shuga 1 na ụdị ọrịa shuga ndị ọzọ, ọkwa ọbara mgbali elu 3 (mgbali ọbara) (mgbali ọbara> 180/100 mm Hg), ị regularụ ọgwụ antihypertensive oge niile, iji ọgwụ antihypertensive mgbe nile, microgoniopathies na-arịa ọrịa shuga (preproliferative na protinerative ọrịa mamịrị retinopathy, ọrịa akụrụ na-adịghị ala ala nke 3b, 4 na 5), CVD (ọrịa obi na-adịghị ala ala, akara nke II - IV (NYHA), ọrịa obi valvular), ọrịa imeju na-adịghị ala ala, ọrịa cancer, ịtụrụ ime, lactation.

Ndị ọrịa niile bịanyere aka na nkwenye siri ike isonye n'ọmụmụ ihe ahụ. Kọmitii na-ahụ maka ụkpụrụ omume nke FSBI GNITsPM nke Ministri Ahụike Russia kwadoro masịrị usoro ọmụmụ a. Protocol nke nzukọ LEK Nke 8 nke 11.29.11.

Na onyonyo onyonyo, ndị ọrịa niile nyochachara nyocha nke ụlọ ọgwụ: nyocha akụkọ ihe mere eme, nyocha ahụike, gụnyere tụọ nha ahụ na ịdị elu ya gbakọọ sọọsọ ahụ (BMI), tụọ systolic (SBP) na ọbara mgbali ọbara (DBP) na ngwaọrụ a kwụnyere. na-eji ubu cuff (HEM-7200 M3, Ahụike Omron, Japan). Ego ọbara mgbalike ka ezumike nkeji iri n'aka nri ọ bụla nọrọ ọdụ n'ọnọdụ 3 ugboro mgbe ọ dị nkeji abụọ, agụnyere ogo atọ na nyocha ahụ. Ewere ọbara maka nnwale ụlọ nyocha (nyocha na biochemical), e dekọtara ECG, wee mee nnwale mmega ahụ na nnwale ahụ site na iji usoro BRUCE (Intertrack, SCHILLER). N'ime ndị ọrịa 250 nyochara, 189 zutere njirisi nyocha. A na-enyocha steeti carbohydrate na ha niile, ekpebiri ogologo telomere na ọrụ telomerase, na edere ike nrụgide nke oxidative na mbufụt na-adịghị ala ala.

Carbohydrate metabolism

E kpebiri ụzọ glucose oxidase na nyocha nke SAPPHIRE-400 na-eji ngwa nyocha DiaSys. Edere ọkwa HbA1c site na mmiri mmiri mmiri na kọmpụta Sapphire 400 (Niigata Mechatronics, Japan) dịka usoro nke onye nrụpụta ọkọlọtọ siri dị.

Nhazi Ogologo Telomere

A na-eme ntụle nke ogologo oge ihe dị ka telomeres nke njikọ nwoke na nwanyị na DNA genomic. N'oge nyocha PCR oge, a na-eme atụmatụ ọnụọgụ nke DNA na usoro telomeric na mkpụrụ ndụ iheom. N’akụkụ abụọ, a rụrụ PCR oge n’eotu mkpụrụ akwụkwọ DNA maka mkpụrụ ndụ ihe omimi. Anyị malitere site na ịdị n'otu nke ọnụ ọgụgụ nke telomeric na otu okike nke nha ka ogologo nke telomeres.

Mmesho nke telomerase

Iji chọpụta ọrụ telomerase, a na-eji usoro nwere ụfọdụ mgbanwe. A nyochachara ọrụ enzyme ahụ na mpempe monocytic ahọrọ nke sel sel (ihe dị ka mkpụrụ ndụ 10,000 na nyocha ọ bụla). E ji obere ihe ndozi mee nkwụghachi nke sel Monocyte, na-ekewapụta ihe ewepụtara. A na-eme mmeghachi omume polylorase telomerase site na mwepụ ahụ; ngwaahịa ndị ahụ enwetara sitere na PCR ozugbo. Onu ogugu nke mmeghachi omume telomerase bu ihe kwesiri ekwesi na oru telomerase (ihe omumu Mastercycler (Eppendorf, Germany).

Ntụlee Oxidative Nchegbu

Iji chọpụta ịdị njọ nke nrụgide oxidative, a na-amụ ịta nke MDA site na usoro nke chemiluminescence na-adabere na luminol na ọbara dum.

Nyocha nke mbufụt na-adịghị ala ala

Iji chọpụta ịdị njọ nke mbufụt na-adịghị ala ala, anyị mụrụ uche fibrinogen, protein protein C-reactive nke ukwuu (CRP) (usoro immunoturbodimetric site na iji nyocha SAPPHIRE-400), IL-6 (usoro immuno-enzyme).

Nnabata ụkpụrụ omume biomedical

Emere ọmụmụ a n'ụzọ kwekọrọ n'ụkpụrụ omume nyocha ọmarịcha na ụkpụrụ nke Nkwupụta Helsinki. Kọmiti Usoro Omume nke ụlọ ọrụ ọgwụgwọ na - ekere òkè dị mma wee kwado usoro ọmụmụ ihe a. Tupu etinye ya na nyocha ahụ

Ndị niile sonyere natara nkwenye ederede ede.

Anyị jiri ngwugwu nke mmemme mgbakọ na mwepụ SAS 9.1 (Sistemu nyocha Anụgụ, SAS Institute Inc., USA). Ejiri data niile banye na tebụl tabular, mgbe nke a mechara nyocha nyocha iji chọpụta njehie ndenye na ụkpụrụ na-efu. Maka oke ọnụọgụ abụọ, ejiri asymmetry ule na kurtosis mee ihe, nke kpughere nkesa zuru oke nke ọtụtụ parameters. A na-egosiputa data bara uru dịka ihe bara uru na ndọpụ ọtọ ọkọlọtọ (M ± SD). E jiri ụkpụrụ abụọ nke ihe nyocha na-adabara tụnyere nke abụọ site na iji nyocha nke oge maka ngbanwe na-aga n'ihu na ogo x2 maka mgbanwe mgbanwe. Maka ihe ngosi ugboro ole, ejiri ihe Studentamụrụ ihe gbanwere na -eche nyocha Fcsher arcsin. Iji chọpụta nha nke mmekọrịta linear n'etiti parampat, emere nyocha mmekọrịta (Spearman rank correlations). Iji chọpụta njikọ dị n'etiti etiti paramita ahụ, e jiri ihe nrita dị icheiche nke nyocha na nyocha nyocha ngwa ngwa. Mgbe ọ tụsịrị ogologo telomere, a na-eme nkesa nke ndị ọrịa ọzọ n'ọnọdụ dabere na oke oke. Otu nke izizi gụnyere ndị ọrịa nwere ogologo telomere dị mkpụmkpụ: site na uru dịkarịrị ala na otu izugbe nke akụkụ nke mbụ (ya bụ, n'okpuru 25% nke ókèala nkesa). Otu nke abụọ gunyere ndị ọrịa nwere ogologo telomere site na nkesa media rue obere nkeji. Otu nke atọ gunyere ndị ọrịa nwere ogologo telomere site na nkesa ọkara wee rue 75% nke ókèala nkesa. E nyere ndị nwere nnukwu telomere buru ibu, nke mejupụtara ihe dị elu na nkuku, kenye ndị otu nke anọ. A jụrụ hypothesis ahụ na p isi na p i ahụghị ihe ịchọrọ? Gbalịa ọrụ nhọrọ akwụkwọ.

Ngụkọta nke ndị ọrịa 189 (ụmụ nwoke 64 na ụmụ nwanyị 125), na-etinye ọnụ na ìgwè abụọ: yana T2DM (i = 50) na enweghị ọrịa shuga (i = 139). Oge oge T2DM bụ 0.9 + 0.089 afọ. Afọ ndụ ndị ọrịa nwere ụdị ọrịa shuga 2 bụ afọ 58.4 ± 7.9, yana otu ndị na - achịkwa - 57.45 + 8.14 afọ (p = 0.48). N'ime otu SD2, SBP bụ 131.76 + 14.7 mm Hg, na otu njikwa - 127.78 + 16.5 mm Hg. (p = 0.13). Ọkwa MDA dị na otu T2DM bụ 3.193 + 0.98 μmol / L, n'ime ndị na-achịkwa ọ bụ 3.195 + 0.82 μmol / L (p = 0.98). Ogo nke IL-6 n'ime otu T2DM bụ 3.37 + 1.14 pg / ml, n'ime ndị na-achịkwa ọ bụ 5.07 + 0.87 pg / ml (p = 0.27).

N'ime ndị ọrịa shuga, ọnụ ọgụgụ ụmụ nwoke dị elu karịa n'ìgwè ndị ahụ siri ike (46% adịrị 29%) (p = 0.013). Nwoke nke nwoke na nwanyị dị na T2DM bụ 46/54% karịa 29/71% na otu njikwa (^ = 0.013). BMI nke ndị ọrịa nwere ụdị shuga 2 dị elu karịa na ndị ahụike siri ike: 30.28 ± 5.42 dị iche 27.68 ± 4.60 kg / m2 (p = 0.002). DBP n'ime otu T2DM bụ 83.02 ± 11.3 mm Hg. vesos 78.6 ± 9.3 mmHg n'ime otu nchịkwa (p = 0.015). N'ime ndị ọrịa nwere ụdị ọrịa shuga 2, ogologo oge nke ọrịa teepulos dị mkpụmkpụ karị (p = 0.031), ọrụ telomerase dị obere (p = 0.039) karịa ndị mmadụ nwere ahụ ike. N'ime otu T2DM, plasma glucose na-ebu ọnụ (GPN) na ọkwa HbA1c dị elu karịa na otu njikwa (p na enweghị ike ịchọta ihe ịchọrọ? Gbalịa ọrụ nhọrọ akwụkwọ.

mer 9.59 + 0.54 9.76 + 0.47 0.031

Telomerase ọrụ 0.47 + 0.40 0.62 + 0.36 0.039

MDA, μmol / L 3.19 + 0.98 3.20 + 0.82 0.98

IL-6, pg / ml 3.37 + 1.14 5.07 + 0.87 0.27

CRP, mg / L 6.34 + 1.06 3.82 + 0.41 0.031

Fibrinogen, g / l 3.57 + 0.87 3.41 + 0,54 0.23

fibrinogen 0.30 + 0.04 0.11 + 0.03 0.004

Tebụl 2. Ndị na-egosi metabolism metabolism, nrụgide oxidative, mbufụt na-adịghị ala ala, ogologo telomere na ọrụ telomerase, dabere na ọnụnọ nke T2DM

SD2 + ("= 50) ___ SD2- (" = 139)

Paramita ogologo ahu-ihe ("= 15) obere ihe - (" = 35) Nrụgo dị ogologo ("= 76) usoro ihe dị mkpụmkpụ (" = 63) P

HbA1c,% 11.54 + 3.57 13.48 + 3.24 0.072 10.98 + 1.83 11.59 + 2.03 0.075

GPN, mmol / L 0.83 + 0.13 0.95 + 0.17 0.02 0.76 + 0.16 0.78 + 0.14 0.59

MDA, μmol / L 2.81 + 0.78 3.35 + 1.04 0.09 3.24 + 0.78 3.14 + 0.87 0.58

CRP, mg / L 3.59 + 0.58 7.39 + 1.47 0.02 3.66 + 0.50 4.07 + 0.68 0.63

Fibrinogen, g / l 3.39 + 0.55 3.70 + 0.91 0.15 3.38 + 0.53 3.44 + 0,55 0.50

Ọnụnọ nke fibrinogen 0.143 0.371 0.09 0.069 0.159 0.09

IL-6, pg / ml 5.95 + 3.89 2.43 + 0.51 0.39 5.70 + 1.31 4.41 + 1.08 0.45

Telomerase ọrụ 0.51 + 0.09 0.47 + 0.08 0.78 0.60 + 0.05 0.66 + 0.07 0.42

Ọrụ telomerase dị ala "0.417 0.710 0.09 0.512 0.474 0.73

Tebụl 3. Ndị na-egosi nrụgide oxidative, mbufụt na-adịghị ala ala na ọrụ telomerase dabere na ogologo telomeres.

Ogologo telomeres Short telomeres

SD2- ("= 15) SD2- (" = 76) P SD2 + ("= 35) SD2- (" = 63) P

MDA, μmol / L 2.81 + 0.78 3.24 + 0.78 0.08 3.35 + 1.04 3.14 + 0.87 0.35

CRP, mg / L 3.59 + 0.58 3.66 + 0.50 0.93 7.39 + 1.47 4.03 + 0.62 0.046

Fibrinogen, g / l 3.39 + 0.55 3.38 + 0.53 0.95 3.70 + 0.91 3.44 + 0,55 0.135

Ọnụnọ nke fibrinogen 0.143 0.069 0.40 0.371 0.159 0.022

IL-6, pg / ml 5.94 + 3.89 5.70 + 1.31 0.94 2.43 + 0.51 4.41 + 1.08 0.10

Telomerase ọrụ 0.51 + 0.09 0.60 + 0.05 0.36 0.47 + 0.08 0.62 + 0.07 0.063

Ọrụ telomerase dị ala "0,512 0.417 0.56 0.710 0.474 0.049

Tebụl 4. Ndị na-egosi metabolism metabolism, nrụgide oxidative, mbufụt na-adịghị ala ala, ogologo telomere na ọrụ telomerase (AT), dabere na ọnụnọ nke T2DM

SD2 + SD2- R

elu AT ala AT P dị elu AT ala AT

HbA1c,% 7.19 + 0.60 7.36 + 0.80 0.45 5.19 + 0.58 5.35 + 0.41 0.16

GPN, mmol / L 7.55 + 1.40 8.47 + 1.79 0.09 5.17 + 0.51 5.33 + 0.44 0.14

MDA, μmol / L 2.93 + 0.90 3.23 + 1.01 0.34 3.06 + 0.93 3.34 + 0.72 0.25

IL-6, pg / ml 2.98 + 1.01 3.91 + 2.03 0.68 3.77 + 1.00 6.37 + 1.80 0.21

CRP, mg / L 5.34 + 1.40 7.12 + 1.76 0.43 4.14 + 0.78 2.55 + 0.26 0.06

Fibrinogen, g / l 3.62 + 0.70 3.66 + 0.85 0.87 3.60 + 0.50 3.37 + 0.43 0.034

Ọnụnọ nke fibrinogen 0.375 0.259 0.43 0.205 0.075 0.09

Ikwu telomere ogologo 9.77 + 0.50 9.43 + 0.42 0.02 9.81 + 0.51 9.70 + 0.45 0.33

ndị ọrịa nwere ahụike n'etiti ndị nwere obere telomeres dị mkpụmkpụ, na “ogologo”, enweghị ọdịiche pụtara ìhè na usoro metabolism, oke nke nrụgide oxidative, na mbufụt na-adịghị ala ala (Isiokwu 2).

N'ime ndị ọrịa nwere T2DM na telomeres dị mkpụmkpụ, ọkwa CRP dị elu ma mụbaa fibrinogen bụ ihe a na-ahụkarị. Achọpụtaghị ọdịiche dị na ọkwa nke MDA, fibrinogen, IL-6. Ihe omumu Telomerase di ala obere n’ime ndi ọrịa nwere oria 2 na obere telomeres (9 = 0.063). Achọpụtara ihe ngosi dị ala nke telomerase n'ime ndị ọrịa nwere T2DM na usoro ahụ “dị mkpụmkpụ” na-adịkarịkarị iche (9 = 0.049).

N'ime ndị nwere telomeres dị ogologo, ihe akara nke mgbu na-adịghị ala ala na nrụgide oxidative, yana ọrụ telomerase, nwere nnwere onwe dị iche iche nke ọnụnọ T2DM (Isiokwu 3).

Ọrụ median telomerase dị 0.50. E kenyere ndị ọrịa niile nwere obere uru ngosipụta a na otu telomerase dị “obere”, yana ndị ọrụ telomerase karịrị nke a, na otu ndị ọrụ telomerase dị elu. N'ime ndị ọrịa nwere ọrịa shuga nke 2, ọnọdụ nke metabolism metabolism, ọrụ nke akara nke nrụgide oxidative na mbufụt na-adịghị ala ala adịghị iche n'etiti otu ndị a, ewezuga telomeres dị mkpụmkpụ na ndị nwere "obere"

telomerase (p = 0.02). Otu njikwa egobeghi ekpughe ihe ndabere nke nrụgide oxidative, CRP na IL-6 na telomerase, na-agbanyeghị, ndị nwere ọrụ telomerase “dị elu” gosipụtara ọkwa fibrinogen dị elu (Isiokwu 4).

N'ime ndị ọrịa T2DM na telomerase “dị ala”, CRP dị elu, ịba ụba fibrinogen bụ ihe kariri, ogologo telomere dị mkpụmkpụ. Ọkwa nke IL-6, MDA na fibrinogen na otu ọrụ telomerase “dị ala” dabere na ọnụnọ nke T2DM. N'ime ìgwè telomerase dị elu "ihu, ihu nwere T2DM + na T2DM adịghị iche na nrụgide oxidative, mbufụt na-adịghị ala ala, na ogologo telomere (Isiokwu 5).

N'ime ndị ọrịa nwere T2DM, achọtara mkpakọrịta n'etiti ogologo telomeres na GPN, CRP, telomerase “dị ala”, mana enweghị mmekọrịta dị n'etiti afọ, ọbara mgbali elu, BMI, HLA1c MDA, fibrinogen, na IL-6 (Isiokwu 6).

N'ime ìgwè CD2 +, a hụrụ mmekọrịta dị mma naanị n'etiti telomerase na ogologo telomere ogologo. N'ime ìgwè na-achịkwa, ọrụ telomerase nwere nke ọma na SBP, DBP, CRP na ọkwa fibrinogen (Isiokwu 7).

Mgbe nke a gasịrị, emere ọtụtụ nyocha linear, ebe eji ogologo telomeres ka ọ dabere na-agbanwe agbanwe, ma ejiri ọgbọ, GPN, CRP, na telomerase dị obere dị ka ihe mgbanwe dị iche iche. Ọ tụgharịrị na naanị GPN na CRP nwere mmekọrịta telomere n'emeghị onwe ha (Isiokwu 8).

Mgbe ị na-eji ọrụ telomerase dị ka ihe ndabere na-agbanwe agbanwe, yana dị ka ndị nọọrọ onwe ha, afọ, DBP, GPN, CRP, na fibrinogen, ọ tụgharịrị na otu CD2, naanị DBP (nzaghachi) na fibrinogen (njikọ a na-eme ugbu a) nwere nnwere onwe na ọrụ telomerase ( okpokoro 9). N'ime otu CD2 +, enweghị mmekọrịta kwụụrụ onwe ya n'etiti paradaịs amụrụ na ọrụ telomerase (Isiokwu 10).

Anyị chọpụtara na ndị ọrịa nwere ọrịa shuga nke 2, ogologo oge nke ahụ mmadụ dị mkpụmkpụ karịa na ndị ahụike. Ọ bụ

Tebụl 6. Ntinye nke telomere nke ogologo na parameters ndị ọzọ na otu ọmụmụ (Spearman ọkwa correlations)

SD2 + (n = 50) SD2- (n = 139) telomere ogologo telomere

Afọ, afọ -0.09, p = 0,52 -0.18, p = 0.035

EGO, mmHg -0.036, p = 0.81 -0.14 p = 0.09

DBP, mmHg 0.066, p = 0.65 -0.03 p = 0.75

BMI, n'arọ / m2 -0.025, p = 0.87 -0.13 p = 0.13

GPN, mmol / L -0.42, p = 0.0027 -0.16 p = 0.05

HbA1c,% -0.23, p = 0.12 -0.03 p = 0.69

MDA, μmol / L -0.17, p = 0.24 0.07, p = 0,55

CRP, mg / L -0.40, p = 0.004 -0.05 p = 0.57

Fibrinogen, g / l -0.18, p = 0.22 -0.04 p = 0.65

IL-6, pg / ml -0.034, p = 0.82 -0.04 p = 0.68

Telomerase ọrụ 0.15, p = 0.33 0.03, p = 0.78

Ọrụ ahụ

merase -0.32, p = 0.035 -0.06, p = 0.61

Tebụl 7. Ntinye nke telomerase na usoro ndị ọzọ na otu ọmụmụ (Spearman rank correlations)

Ọrụ nke telomerase SD2 + (n = 50) SD2- (n = 139)

Afọ, afọ nke GARDEN, mm Hg DBP, mmHg BMI, kg / m2 GPN, mmol / L НАА1с,% MDA, μmol / L SRB, mg / L

Ọnụnọ nke CRP Fibrinogen mụbara, g / l IL-6, PG / ml

Ọdịmma nke ahụ

Ahụ toro ogologo

5, p = 0.35 2, p = 0.44 4, p = 0.37 -0.07, p = 0.65 -014, p = 0.38 -0.08, p = 0.64 - 0.064, p = 0.69 0.056, p = 0.73 0.03, p = 0.89-0.086, p = 0,59-0.006, p = 0.97

0.07, p = 0,52 0.20, p = 0.08 0.33, p = 0.003

-0,04 -0,17 -0,08 -0,11

p = 0.72 p = 0.14 p = 0.47 p = 0.47

0.11, p = 0.35 0.35, p = 0.002 0.28, p = 0.01 -0.19, p = 0.12

0.15, p = 0.33 0.03, p = 0.78 0.40, p = 0.0095 0.14, p = 0.22

kwekọrọ na nsonaazụ ndị ọzọ dere. Agbanyeghị, n'ọmụmụ ihe M. Sampson et al. ahụghị mmekọrịta dị n'etiti mkpụmkpụ nke ogologo tebul nke lymphocytic na ndị na-egosi metabolism metabolism (ikekwe n'ihi ọnụ ọgụgụ dị nta nke

Tebụl 5. Ndị na-egosi nrụgide oxidative, mbufụt na-adịghị ala ala na ogologo oge telomeres dabere na ọrụ telomerase (AT)

Parameter ala AT High AT

SD2 + SD2- r SD2 + SD2- r

MDA, μmol / L 3.23 + 1.01 3.34 + 0.72 0.68 2.93 + 0.90 3.06 + 0.93 0.68

IL-6, pg / ml 3.91 + 2.03 6.37 + 1.80 0.37 2.98 + 1.01 3.77 + 1.00 0.62

CRP, mg / L 7.12 + 1.76 2.55 + 0.26 0.016 5.34 + 1.40 4.14 + 0.78 0.44

Fibrinogen, g / l 3.66 + 0.85 3.37 + 0.43 0.11 3.62 + 0.70 3.60 + 0.50 0.90

Ọnụnọ nke fibrinogen 0.259 0.075 0.043 0.375 0.205 0.21

Ikwu telomere ogologo 9.43 + 0.42 9.70 + 0.45 0.016 9.77 + 0.50 9.81 + 0.51 0.80

Tebụl 8. Depdabere na telomere ogologo na afọ, GPN, CRP, belatara ihe telomerase dị ka mgbanwe nke onwe na ndị ọrịa nwere ụdị ọrịa shuga 2.

Nkata B Standard njehie P

Afọ, afọ -0.0008 -0.008 0.92

GPN, mmol / L -0.076 0.036 0.004

CRP, mg / L -0.018 0.007 0.020

Ọrụ telome dị ala

ugboro -0.201 0.125 0.116

Tebụl 9. Ndabere na ọrụ telomerase dị afọ, DBP, GPN, CRP, fibrinogen, GPN dị ka ndị iche iche nọọrọ onwe ha na otu njikwa.

Nkata B Standard njehie P

Afọ, afọ -0.003 0.005 0.534

DBP, mmHg -0.010 0.004 0.012

GPN, mmol / L -0.105 0.081 0.20

CRP, mg / L 0.019 0.010 0.073

Fibrinogen, g / l 0.205 0.080 0.013

Tebụl 10. Ndabere na ọrụ telomerase dị afọ, DBP, GPN, CRP, fibrinogen, GPN dị ka ndị mgbanwe dịịrị onwe ha na otu ndị ọrịa nwere ụdị shuga 2.

Nkata B Standard njehie P

Afọ, afọ 0.002 0.008 0.74

DBP, mmHg -0.0001 0.006 0.98

GPN, mmol / L -0.006 0.039 0.15

CRP, mg / L 0.007 0.009 0.45

Fibrinogen, g / l -0.009 0.089 0.91

STI otu). Ọmụmụ ihe anyị kpughere ọdịiche pụtara ìhè na HbA1c na GPN n'ime ndị ọrịa nwere T2DM nwere telomeres “ogologo” na “mkpụmkpụ,” ha chọpụtakwara mmekọrịta na-adịghị mma n'etiti ogologo telomere na GPN. Enwere ike ịrụ ụka na n'ime ndị ọrịa nwere ụdị shuga 2, telomeres dị mkpụmkpụ na njikwa shuga na-adịghị mma, na hyperglycemia, n'aka nke ya, nwere ike imebi ihe na-emebi ihe gbasara ịka nká.

Anyị chọpụtara na ọrụ telomerase n'ime ndị ọrịa nwere ụdị shuga 2 dị ala karịa ndị ahụ siri ike, nke kwekọrọ na data ole na ole dị. Ọrụ nke telomerase na usoro nke ịka nká bụ ihe gbara ọkpụrụkpụ ma amụtachaghị nke ọma. Egosipụtala mmekọrịta dị n'etiti ọrụ telomerase na ogologo telomere, nke kwekọrọ n'echiche na ọrụ nke telomerase adịghị mkpa iji nọgide na-enwe telomere ogologo homeostasis na agadi.

A na-ahụta mmetụta mbibi hyperglycemia na ihe omimi nke telomeres, gụnyere na mkpụrụ ndụ endothelial, site na usoro nrụgide oxidative na mbufụt na-adịghị ala ala. Ma, odi nkpa

Enweghị ọdịiche dị na ọkwa MDA n'etiti otu dị iche iche nke T2DM + na T2DM (ikekwe n'ihi ntakịrị oge nke ọrịa shuga na enweghị ọnya ọnya na-adịghị ala ala, ebe ọ bụ na a na-ejikọ hyperglycemia ogologo oge na mmepe nke nrụgide oxidative siri ike na nke na-adịgide adịgide). Ọ nwere ike ịdị mkpa iji ihe ngosi ndị ziri ezi karịa nrụgide oxidative, dịka urinary excretion nke 8-iso-prostaglandin F2a. Anyị hụrụ ọkwa dị elu nke akara mkpali na ndị ọrịa nwere ụdị ọrịa shuga 2 karịa ka ndị mmadụ n'otu n'otu. Akara ọzọ nke na-akpata mkpamkpa, IL-6, dịka e kpughere ya na nso nso a, nwere ọtụtụ mmetụta, ebe ọ bụghị naanị cytokine, kamakwa myokine, na-akpali myogenesis ma na-emetụta oke metabolism ike. Ikekwe ọ bụ ya mere ọkwa nke IL-6 dị na njikwa ji wee dịtụ elu, nke, agbanyeghị, chọrọ ọmụmụ ihe ọzọ.

Ọrịa ọgbụgba na-ebute ịka nká nke mkpụrụ ndụ, telomere dị mkpụmkpụ site na ịgbalite mmụba nke sel lymphocytic na ịgbalite ntọhapụ nke ROS, na-akpata mmebi oxidative n'akụkụ akụkụ ọnụ nke DNA. Na 2012, emere ka ekpughere ya na mbelata nke telomeres na-abawanye na oge T2DM nwere ike jikọtara ya na mmụba yiri nke ahụ na-egbu ume na mbufụt. Nsonaazụ anyị dabere na data sitere n'ọmụmụ gara aga. Anyị chọpụtara ọkwa CRP dị elu na nke MDA dịtụ elu na ndị ọrịa nwere ụdị shuga 2 na telomeres dị mkpụmkpụ karịa ndị ọrịa nwere ogologo telomeres. Enwere mmekọrịta na-adịghị mma n'etiti ogologo oge nke lymphocyte telomere na akara akara aka na-arịa ọrịa na-adịghị ala ala - CRP, nke na-egosi itinye aka na mbufụt na-adịghị ala ala na telomere na-eme ka ndị ọrịa nwere ụdị ọrịa 2 dị ala. N'ime otu nchịkwa ahụ, enweghị njikọ n'etiti CRP na ogologo telomere, nke kwekọrọ na nsonaazụ nke ọmụmụ ndị ọzọ. Enwere ike ịkọwa enweghị mkparịta ụka n'etiti IL-6, fibrinogen, na telomere ogologo na otu abụọ site na obere mgbanwe nke ndị na-egosi ihe ndị a. Ọzọkwa, ịdabere naanị n'ogo nke na-ekesa cytokines, mmadụ ga-elelị ogo mbufụt mpaghara na anụ ahụ.

Ihe omuma banyere akwukwo banyere mmekpa ahu mmadu na telomerase bu ihe di iche. Ọrịa nwa oge na-ebute ọrịa telomerase, nke anyị chọpụtara na ndị ọrịa nwere ụdị shuga nke 2. Site na mkpasu iwe na-adịchaghị ala, dịkwa ka nke metabolic syndrome ma ọ bụ na-adịghị ala ala atherosclerosis, na ntụle, enwere ịrị elu na telomerase, nke nwere ike ịkwụ ụgwọ na okike, na-agbada mbelata telomere ogologo oge na-ekesa mkpụrụ ndụ

n'okpuru nduzi nke cytokines na-akpata mkpali. N'ezie, n'ime ìgwè ndị na-achịkwa, anyị chọpụtara mmekọrịta dị mma n'etiti ọrụ telomerase na akara nke ọnya na-adịghị ala ala.

Ọ dị mkpa imesi ya ike na, dị ka data anyị si dị, ọkwa nke nrụgide oxidative, mbufụt na-adịghị ala ala na ọrụ telomerase n'ime ndị ọrịa nwere T2DM na telomeres “ogologo oge” adịghị iche na atụmatụ ndị kwekọrọ na ndị ahụ ike. Enwere ike iche na site na obere oge T2DM, mkpụrụ ndụ ihe gbara afọ ga-eche ogologo oge telomere na-echebe ndị ọrịa site na mmebi nke nrụgide oxidative na mbufụt na-adịghị ala ala, na-enye mweghachi nke anụ ahụ ndị mebiri emebi, gụnyere arịa ọbara. N'ụzọ dị iche, n'ime ndị ọrịa nwere telomere T2DM na "mkpụmkpụ mkpirikpi," n'agbanyeghị obere oge ọrịa ahụ, ogo nke mbufụt na-adịghị ala ala na ogo nke mbelata ọrụ telomerase dị mkpa karịa. Ekwesịrị iburu n'uche na ndị ọrịa nke nwere ụdị ọrịa shuga 2 na nchịkwa ya bụ ndị nhata n'oge afọ.

Enwere ihe akaebe na-eto eto na mbelata nke telomere bụ isi ihe dị na mbenata mbelata mkpụrụ ndụ na nbilata anụ ahụ metụtara afọ. Njikọ nke T2DM na usoro nke ịka nká na ogo nke mbufụt na-adịghị ala ala na nrụgide oxidative nwere ike ịkọwa ihe dị elu nke CVD na ọrịa a. Ọmụmụ ihe ndị ọzọ ga-enye ohere iburu n'uche telomere ogologo n'etiti ndị ọrịa nwere ọrịa shuga 2, otu ndị chọrọ nchịkwa ike nke metabolism metabolism, nke ga-enye ụzọ kachasị maka ọgwụgwọ nke ọrịa ahụ.

1. N'ime ndị ọrịa nwere ọrịa shuga nke 2, ogologo telomere dị mkpụmkpụ, ọrụ telomerase dịkwa obere karịa na ndị nwere ahụike. Egosighi ụkpụrụ nke arụ ahụ-merase na ịgbanwe ogologo telomeres.

2. Ọkwa MDA n’ebe ndị ọrịa nwere ụdị shuga 2 na ndị ahụ gbasiri ike ma ọ bụrụ otu. A na-ekwupụta ọrịa na-adịghị ala ala karịa ndị ọrịa nwere ụdị ọrịa shuga 2 karịa ndị nwere ahụike nke ọgbọ. Ọrịa na-adịghị ala ala na-ebute ụzọ n'ịbelata telomeres na ịba ụba ọrụ telomerase.

3. N'ime ndị ọrịa nwere T2DM na telomeres “ogologo oge”, nrụgide nrụgide oxidative na mbufụt na-adịghị ala ala adịghị iche na ọnụego kwekọrọ na ndị mmadụ nwere ahụ ike.

4. N'ime ndị ọrịa nwere T2DM, telomeres “dị mkpụmkpụ” na-ejikọta ya na nchịkwa ọrịa shuga na-adịghị mma na ọrịa na-adịghị ala ala nke ukwuu.

5. “Ogologo oge” telomeres na-echebe ndị ọrịa shuga site na mmebi nke nrụgide oxidative na mbufụt na-adịghị ala ala.

Enweghị esemokwu nke mmasị.

Emere ọmụmụ a dịka akụkụ nke ọrụ nke steeti "Ọmụmụ ihe banyere usoro ihe eji eme ihe na atherogenesis iji wee mepụta ụzọ maka nchọpụta izizi nke atherosclerosis dị ka usoro isi ọwụwa pathophysiological maka mmepe nke ọrịa obi na nsogbu ha."

Echiche nyocha na imewe - E.N. Dudinskaya, O.N. Tkacheva, I.D. Strazhesko, E.V. Akasheva.

Nchịkọta na nhazi nke ihe - N.V. Brailova, E.V. Plohova, V.S. Pihtina.

Nhazi data ndekọ - V.A. Uru.

Ederede ederede - N.V. Brailova.

Na - edezi - E.N. Dudinskaya, O.N. Tkacheva, M.V. Shestakova, S.A. Ndị na-alụ ọgụ.

Ndi otu ndi n’ekele akwukwo dere ekele A.S. Kruglikov, I.N. Ozerov, N.V. Gomyranova (Instlọ Ọrụ Mmefu Ego nke Federal "Statelọ Ọrụ Nnyocha Ọchịchị Maka Mgbochi Ọgwụ" nke Ministry of Health of the Russian Federation) na D.A. Skvortsov (Institute of Physical and Chemical Biology, onye aha ya bu AN Belozersky GBOU VPO MSU nke aha ya bu MV Lomonosov) maka enyemaka n’ duzie ihe omumu a.

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