Современные аспекты патогенеза сахарного диабета 1 типа
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Обзоры литературы Современные аспекты патогенеза сахарного диабета 1 типа í.Ç. çËÍÓÌÓ‚‡ Éì ù̉ÓÍËÌÓÎӄ˘ÂÒÍËÈ Ì‡Û˜Ì˚È ˆÂÌÚ (‰Ë. – ‡Í‡‰. êÄç Ë êÄåç à.à. щӂ) êÄåç, åÓÒÍ‚‡ ‡Ë·ÓΠÔÓÔÛÎflÌÓÈ ÚÂÓËÂÈ Ô‡ÚÓ„ÂÌÂÁ‡ Ò‡ı‡ÌÓ„Ó ‰Ë‡·ÂÚ‡ (ëÑ) 1 ÚËÔ‡ ‚ Ú˜ÂÌË ÔÓÒΉÌËı 20 ÎÂÚ fl‚Îfl·Ҹ ÚÂÓËfl, Ô‰ÎÓÊÂÌ̇fl ‚ 1986 „. G. Eisenbarth [16]. ëӄ·ÒÌÓ ˝ÚÓÈ ÍÓ̈ÂÔˆËË ëÑ 1 ÚËÔ‡ ‡Á‚Ë‚‡ÂÚÒfl Û „ÂÌÂÚ˘ÂÒÍË Ô‰‡ÒÔÓÎÓÊÂÌÌ˚ı Îˈ. àÌˈˇÚÓ‡Ï Ì‡˜‡Î‡ ‡ÛÚÓËÏÏÛÌÌ˚ı ÔÓˆÂÒÒÓ‚ fl‚Îfl˛ÚÒfl Ù‡ÍÚÓ˚ ‚̯ÌÂÈ Ò‰˚. 燘‡Î¸Ì‡fl ÒÚ‡‰Ëfl ëÑ 1 ÚËÔ‡ – „Ë·Âθ ÓÒÚÓ‚ÍÓ‚˚ı ÍÎÂÚÓÍ – ÔÓÚÂ͇ÂÚ ·ÂÒÒËÏÔÚÓÏÌÓ, ÌÓ ÏÓÊÂÚ ·˚Ú¸ ‚˚fl‚ÎÂ̇ Ò ÔÓÏÓ˘¸˛ ÓÔ‰ÂÎÂÌËfl ‡ÛÚÓ‡ÌÚËÚÂÎ. íÓθÍÓ Ì‡ ÔÓÒΉÌËı ÒÚ‡‰Ëflı ÔÓˆÂÒÒ‡, ÍÓ„‰‡ ÔÓ‰‡‚Îfl˛˘Â ·Óθ¯ËÌÒÚ‚Ó β-ÍÎÂÚÓÍ ÔÓ„Ë·‡ÂÚ Ë ‚ÓÁÌË͇ÂÚ ‡·ÒÓβÚ̇fl ̉ÓÒÚ‡ÚÓ˜ÌÓÒÚ¸ ËÌÒÛÎË̇, ÔÓfl‚Îfl˛ÚÒfl ÍÎËÌ˘ÂÒÍË ÔËÁ̇ÍË ‰Ë‡·ÂÚ‡ (ËÒ. 1). Ç Ì‡˜‡Î 1970-ı „Ó‰Ó‚ ËÒÒΉӂ‡ÌËfl, Ôӂ‰ÂÌÌ˚ J.Nerup Ë ‰. Û˜ÂÌ˚ÏË, ÔÓ͇Á‡ÎË ‚Á‡ËÏÓÒ‚flÁ¸ ÒËÒÚÂÏ˚ HLA Ë Á‡·Ó΂‡ÂÏÓÒÚË ëÑ 1 ÚËÔ‡ [33]. àÁ̇˜‡Î¸ÌÓ „ÂÌÂÚË͇ ëÑ 1 ÚËÔ‡ Ô‰ÒÚ‡‚Îfl·Ҹ ÓÚÌÓÒËÚÂθÌÓ ÔÓÒÚÓÈ: ÔË Ì‡Î˘ËË ÓÔ‰ÂÎÂÌÌ˚ı ‡ÎÎÂÎÂÈ „ÂÌÓ‚ ÒËÒÚÂÏ˚ HLA ‰ÓÏËÌËÓ‚‡ÌË Á‡·Ó΂‡ÌËfl ·˚ÎÓ Ô‡ÍÚ˘ÂÒÍË ÔÓÎÌ˚Ï [32]. á‡ÚÂÏ Ô˯ÎÓ ÔÓÌËχÌËÂ Ú‡Í Ì‡Á˚‚‡ÂÏÓ„Ó «„ÂÌÂÚ˘ÂÒÍÓ„Ó Íӯχ‡» ‰Ë‡·ÂÚ‡ 1 ÚËÔ‡ [35]. ç‡ Ò„ӉÌfl¯ÌËÈ ‰Â̸ ËÁ‚ÂÒÚÌÓ ·ÓΠ‰‚Ûı ‰ÂÒflÚÍÓ‚ ÎÓÍÛÒÓ‚ Ë 100 „ÂÌÓ‚-͇̉ˉ‡ÚÓ‚, Ëϲ˘Ëı ‡Á΢ÌÛ˛ ÒÚÂÔÂ̸ ‚ÎËflÌËfl ̇ ‡Á‚ËÚË ëÑ 1 ÚËÔ‡ [24,41] (Ú‡·Î. 1, 2). ç ç‡ ÔÓÚflÊÂÌËË ÔÓÒΉÌËı ‰ÂÒflÚËÎÂÚËÈ ·˚ÎÓ ËÒÒΉӂ‡ÌÓ ÏÌÓÊÂÒÚ‚Ó Ù‡ÍÚÓÓ‚ ÓÍÛʇ˛˘ÂÈ Ò‰˚ Ò ˆÂθ˛ ‚˚fl‚ÎÂÌËfl ‰ÓÒÚÓ‚ÂÌÓ„Ó Í‡Ì‰Ë‰‡Ú‡, ‚ÎËfl˛˘Â„Ó Ì‡ Á‡·Ó΂‡ÌË ëÑ 1 ÚËÔ‡ [2]. ç‡ Ô‚˚ı ÔÓ‡ı Ú‡ÍËÏË Í‡Ì‰Ë‰‡Ú‡ÏË Ò˜ËÚ‡ÎËÒ¸ ‚ËÛÒ˚ [23]. Ç Ì‡˜‡ÎÂ Ë Ò‰ËÌ 80-ı „Ó‰Ó‚ ÔÓ¯ÎÓ„Ó ÒÚÓÎÂÚËfl Û͇Á˚‚‡ÎÓÒ¸ ̇ Á̇˜ÂÌË ÔÓ‰ÓÎÊËÚÂθÌÓÒÚË „Û‰ÌÓ„Ó ‚Ò͇ÏÎË‚‡ÌËfl [11]. Ç Í‡˜ÂÒÚ‚Â Ô˘ËÌ˚ Á‡·Ó΂‡ÌËfl ̇Á˚‚‡ÎÓÒ¸ ÛÔÓÚ·ÎÂÌË ÍÓÓ‚¸Â„Ó ÏÓÎÓ͇ ËÎË ËÒÍÛÒÒÚ‚ÂÌÌÓ ‚Ò͇ÏÎË‚‡ÌË [14,30]. é‰Ì‡ÍÓ ËÒÒΉӂ‡ÌËÂ, Ôӂ‰ÂÌÌÓ ‚ 2003 „. å.Ä. Atkinson [6], Ì ÔӉڂ‰ËÎÓ ÚÓÚ Ù‡ÍÚ, ˜ÚÓ 100% ÒÛ·˙ÂÍÚÓ‚, ÒÚ‡‰‡˛˘Ëı ëÑ 1 ÚËÔ‡, ËÏÂ˛Ú ‡ÌÚËÚ· ÔÓÚË‚ ÏÓÎÂÍÛÎ˚ BSA (bovine serum albumin) [25]. èÓ ÔÓÒΉÌËÏ ‰‡ÌÌ˚Ï, ‡Á‚ËÚË ‡ÌÚË-β-ÍÎÂÚÓ˜ÌÓ„Ó ‡ÛÚÓËÏÏÛÌËÚÂÚ‡ Ò‚flÁ‡ÌÓ Ò ‚˚·ÓÓÏ ‚ÂÏÂÌË ‚Íβ˜ÂÌËfl ‚ ‡ˆËÓÌ ÔËÚ‡ÌËfl Ï·‰Â̈‚ ÁÂÌÓ‚˚ı [8,34,42], ÛÔÓÚ·ÎÂÌË Á‡ÏÂÌËÚÂÎÂÈ Ò‡ı‡‡, ÍÓÙÂË̇ Ë ‰‡Ê ÍÓÔ˜ÂÌÓÈ ˚·˚ [4]. LJÊ̇fl Óθ ÓÚ‚Ó‰ËÚÒfl ÔËÓ‰ÌÓÏÛ ÍÓÏÔÓÌÂÌÚÛ; ÏÂÊ‰Û ‡Á΢Ì˚ÏË Â„ËÓ̇ÏË Ïˇ ̇·Î˛‰‡ÂÚÒfl ‡ÁÌˈ‡ ‚ ˜‡ÒÚÓÚ Á‡·Ó΂‡ÂÏÓÒÚË ëÑ 1 ÚËÔ‡ ‰Ó 500 ‡Á [29,39]. Ç 1974 „. ·˚· ÓÔÛ·ÎËÍÓ‚‡Ì‡ ÒÚ‡Ú¸fl G.F. Bottazzo Ò ÓÔËÒ‡ÌËÂÏ ‡ÌÚËÚÂÎ Í ÓÒÚÓ‚ÍÓ‚˚Ï ÍÎÂÚÍ‡Ï (ICA) [12]. àÏÂÌÌÓ ˝Ú‡ ‰‡Ú‡ ÔËÁ̇ÂÚÒfl ÏÌÓ„ËÏË Í‡Í ‰‡Ú‡ ÛÒÚ‡ÌÓ‚ÎÂÌËfl ‡ÛÚÓËÏÏÛÌÌÓ„Ó ı‡‡ÍÚ‡ ëÑ 1 ÚËÔ‡. Предполагаемый фактор внешней среды Масса β-клеток ? Клиническое начало Стадия 4 Нарушение метаболизма глюкозы НТГ (ОГТТ) ? Стадия 1 Генетическая предрасположенность Стадия 2 Аутоимность Восприимчивые гены Гуморальные аутоантитела Стадия 5 Клинический диабет Стадия 6 Полная гибель β-клеток Стадия 3 Метаболический дефект Потеря 1 фазы секреции инсулина (ВГТТ) Время Рис. 1. Стадии развития сахарного диабета 1 типа. 3/2006 59 Обзоры литературы Сахарный диабет Таблица 1 Генетика CД типа 1 Локусы HMO Md9.1 HMO Idd9.2 HMO Idd9.3 HMO Idd10 HMOJdd18 Unnamed chromosome 1 IDDM7 IDDM12 HMO Idd5.2 IDDM13 IDDM9 HMO Idd3 IDDM18 IDDM1 IDDM15 IDDM5 IDDM8 HMO Idd9.4 IDDM10 IDDM17 IDDM2 IDDM4 IDDM11 IDDM3 Unnamed chromosome 16 HMO Idd4 IDDM16 Регион 1p34.3 1p36.21-36.22 1p36.22-46.23 1pl2 1p 13.2-13.3 1q42.2 2q32.2 2q33.3 2q35-36.1 2q36.1 D3S1303 4q27.28.1 5q3 1.2-35.1 6p21.31 6q22.1 6q23.3-25.3 6q26-27 9p21.3-22.1 10pll-qll 10qj26.l-26.il Ilpl5.5 Ilql2.2-13.1 14q31.3-32.13 15q26.1-26.2 16q24.1 17ql2-21.1 18ql2.3-22.1 ÅÓΠ˜ÂÏ 30 ÎÂÚ ÚÂÒÚ˚ ̇ ICA ÓÒÚ‡‚‡ÎËÒ¸ Ó‰ÌËÏ ËÁ ÓÒÌÓ‚Ì˚ı ÏÂÚÓ‰Ó‚ ËÒÒΉӂ‡ÌËfl ÔË ËÁÛ˜ÂÌËË ëÑ 1 ÚËÔ‡. чÌÌ˚È ÏÂÚÓ‰ Ó͇Á‡ÎÒfl ̇˷ÓΠۉ‡˜Ì˚Ï Í‡Í ‚ ‰Ë‡„ÌÓÒÚËÍ Á‡·Ó΂‡ÌËfl, Ú‡Í Ë ÔË ‚˚fl‚ÎÂÌËË Îˈ Ò ÔÓ‚˚¯ÂÌÌ˚Ï ËÒÍÓÏ ‡Á‚ËÚËfl ‰Ë‡·ÂÚ‡. àÒÒΉӂ‡ÌËfl, ÔÓÒ‚fl˘ÂÌÌ˚ ÔÓÙË·ÍÚËÍ Á‡·Ó΂‡ÌËfl, ·˚ÎË ·˚ Ì‚ÓÁÏÓÊÌ˚ ·ÂÁ ÓÔ‰ÂÎÂÌËfl ICA. é‰Ì‡ÍÓ ‚ ̇ÒÚÓfl˘Â ‚ÂÏfl Ò˜ËÚ‡ÂÚÒfl, ˜ÚÓ Ô‚˘Ì˚Ï „ÛÏӇθÌ˚Ï Ï‡ÍÂÓÏ fl‚Îfl˛ÚÒfl ‡ÛÚÓ‡ÌÚËÚ· Í ÏÓÎÂÍÛΠËÌÒÛÎË̇, ‡ Ì ICA [3,17]. ÄÛÚÓ‡ÌÚËÚ· Í ËÌÒÛÎËÌÛ (IAA) ı‡‡ÍÚÂËÁÛ˛ÚÒfl ‚˚ÒÓÍÓÈ ˜Û‚ÒÚ‚ËÚÂθÌÓÒÚ¸˛, ‡ÌÌËÏ ÔÓfl‚ÎÂÌËÂÏ Ë ·˚ÒÚ˚Ï ËÒ˜ÂÁÌÓ‚ÂÌËÂÏ. àı ͇ÚÍÓ‚ÂÏÂÌÌÓ ÔÓfl‚ÎÂÌË ÏÓÊÂÚ ·˚Ú¸ χÍÂÓÏ Ó·Ì‡ÛÊÂÌËfl ‰Û„Ëı ‡ÌÚËÚÂÎ ‚ ·ÓΠÔÓÁ‰ÌË ÒÓÍË. Ç ˆÂÎflı ÔÓ‚˚¯ÂÌËfl ‰ÓÒÚÓ‚ÂÌÓÒÚË ÂÁÛθڇÚÓ‚ ÌÂÓ·ıÓ‰ËÏÓ ËÒÔÓθÁÓ‚‡ÌË ‡Á΢Ì˚ı „ÛÔÔ ‡ÌÚËÚÂÎ. ëÙÓÏËÓ‚‡ÎÓÒ¸ ÏÌÂÌËÂ, ˜ÚÓ ÒËÏÔÚÓÏ˚ ëÑ 1 ÚËÔ‡ Ó·˚˜ÌÓ ÔÓfl‚Îfl˛ÚÒfl, ÍÓ„‰‡ 90–95% β-ÍÎÂÚÓÍ ÔÓ„Ë·ÎË [15]. àÒÒΉӂ‡ÌËfl ‰ÓÍÚÓ‡ W. Gepts, Ôӂ‰ÂÌÌ˚ ̇ Ô‡ÚÓÎӄӇ̇ڇÏ˘ÂÒÍÓÏ Ï‡Ú¡ÎÂ, ˜‡ÒÚ˘ÌÓ ÔÓ‰Ú‚Âʉ‡˛Ú ˝ÚÓÚ Ù‡ÍÚ [18]. íÂÏ Ì ÏÂÌÂÂ, Í‡Í ÔÓ͇Á‡ÎË ÔÓÒΉÌË ËÒÒΉӂ‡ÌËfl, ÒÂ͈Ëfl ËÌÒÛÎË̇ ‚ ıӉ ÚÂÒÚÓ‚ ÒÓ Òϯ‡ÌÌ˚Ï ÔËÚ‡ÌËÂÏ Û ·ÓθÌ˚ı Ò ‚Ô‚˚ ‚˚fl‚ÎÂÌÌ˚Ï ëÑ ÒÓÒÚ‡‚ÎflÂÚ ÔÓÎÓ‚ËÌÛ ÔÓ Ò‡‚ÌÂÌ˲ Ò ÍÓÌÚÓθÌÓÈ „ÛÔÔÓÈ Á‰ÓÓ‚˚ı β‰ÂÈ [40]. óÂÎÓ‚ÂÍ 60 3/2006 Таблица 2 Генетика CД типа 1 (гены-кандидаты) ACE ADAM33 AGT AIRE ALDRL2 APOE AR B2M B7 BAT2 BCL2 in IDDM6 CASP10 Idd5.2 CASP7 in IDDM17 CASP8 CBLB CCR5 CD14 CD28 in IDDM12 CD4 CD48 CD80 CD8G CFLAR CP in IDDM9 CRP CTLA4 in IDDM12 CXCL12 in IDDM10 CYP27B1 ERVK2 ERVK3 FABP2 GAD2 in IDDM10 GCK GLP1R IISD11B2 IISPG2 IAM4L1 ICAM1 ICOSL IFNG IGF1 IL10 IL12A in IDDM9 IL12B in IDDM18 IL13 IL18 IL18BP ILIA IL1RN NFKB1 NOS3 PSMB8 in IDDM1 PTPN22 PTPRC REG1A PADI4 PDCD1LG1 PPARG REG1B SLAMF1 SLC11A1 in IIMO IL21R IL2RA IL2RB IL2RG IL4 IL4R IL6 IL8 INS in IDDM2 IRF1 IRS1 KCNJ11 KIR2DS2 KIR3DL1 KLRC4 LAGS LCK in IIMO Idd9.1 LCT LRP5 in LDDM4 MBL2 MHC2TA MICA MRC1 NAT2 NEUROD1 TAP2 in IDDM1 TCF7 TGFB1 TLR1 TLR10 TLR2 TLR3 TLR4 TLR6 TLR7 TLR8 TLR9 TNF TNFRSFllAinIDDM6 TNFRSF18 TNFRSF1A TNFSF11 TNFSF5 TNFSF6 TNFSF9 TREM2 TYROBP VDR ÔË ÓʉÂÌËË ËÏÂÂÚ 100% ËÎË ÔÓ˜ÚË 100% «ÌÓχθÌ˚» Ò‚ÓËı β-ÍÎÂÚÓÍ. ÑÓ Ì‡ÒÚÓfl˘Â„Ó ‚ÂÏÂÌË ‚ ÒËÎÛ Ô‡ÍÚ˘ÂÒÍËı ÚÛ‰ÌÓÒÚÂÈ ‚Ò ¢ Ì‚ÓÁÏÓÊÌÓ ÚÓ˜ÌÓ ÓÔ‰ÂÎËÚ¸ Û ˜ÂÎÓ‚Â͇ ÓÒÚÓ‚ÍÓ‚Û˛ ÍÎÂÚÓ˜ÌÛ˛ χÒÒÛ in vivo ËÎË ex vivo, ‚ ÓÔÛ·ÎËÍÓ‚‡ÌÌÓÈ ÔÓ ‰‡ÌÌÓÏÛ ‚ÓÔÓÒÛ ÎËÚ‡ÚÛ ڇÍʉ ÏÌÓ„Ó ‡ÒıÓʉÂÌËÈ [8]. çÂÔÓÌflÚÌÓ, ͇ÍÓ‚ „‡‰ËÂÌÚ «Ô‡‰ÂÌËfl» β-ÍÎÂÚÓÍ, ÌÓÒËÚ ÎË ÓÌ ÎËÌÂÈÌ˚È ı‡‡ÍÚÂ; ËϲÚÒfl ÎË ‚ ̇˜‡Î¸ÌÓÈ ÒÚ‡‰ËË ÔÂËÓ‰˚ ÒÚÛÔÂ̘‡ÚÓÈ ÂÏËÒÒËË, ÏÓÊÂÚ ÎË ÔÓËÒıÓ‰ËÚ¸ ÔÓˆÂÒÒ Â„Â̇ˆËË β-ÍÎÂÚÓÍ [19,21]; ͇ÍÓ‚Ó ‚ÎËflÌË هÍÚÓÓ‚ ‚ÓÁ‡ÒÚ‡, ÔÓ· Ë „ÂÌÂÚËÍË Ì‡ ˝ÚÓÚ „‡‰ËÂÌÚ, Ë ÍÓ„‰‡ ‰‡ÌÌ˚È ÔÓˆÂÒÒ Ì‡˜Ë̇ÂÚÒfl. ç‡ÍÓ̈, Íβ˜Â‚ÓÈ ÔÓ·ÎÂÏÓÈ, ÓÒÓ·ÂÌÌÓ ‰Îfl ËÏÏÛÌÓÎÓ„Ó‚, ÓÒÚ‡ÂÚÒfl ÌÂÓ·ıÓ‰ËÏÓÒÚ¸ ‚˚flÒÌÂÌËfl ‚ÓÔÓÒ‡, ÔÓ˜ÂÏÛ ‡ÁÛ¯ÂÌË β-ÍÎÂÚÓÍ Ó·˚˜ÌÓ ÔÓËÒ- Обзоры литературы Сахарный диабет Факторы внешнй среды Масса β-клеток Иммунная дисрегуляция IAA GADA ICA 512A ICA Взаимодействия между генами, передающими восприимчивость и сопротивляемость Вариабельность инсулитов, чувствительность β-клеток к повреждению Потеря I фазы инсулинового ответа (в/в ГТТ) Интолерантность к глюкозе Время Предиабет Клинически явный диабет СД Снижение С-пептида ниже уровня определения Рис. 2. Современная модель патогенеза диабета 1 типа (Atkinson M.A., Eisenbarth G., Diabetes, 2005). ıÓ‰ËÚ Ï‰ÎÂÌÌÓ Ë Á‡ÌËχÂÚ ÔÂËÓ‰ ÓÚ ÌÂÒÍÓθÍËı ÏÂÒflˆÂ‚ ‰Ó ÌÂÒÍÓθÍËı ÎÂÚ, ‡ ÚÓ Ë ‰ÂÒflÚËÎÂÚËÈ, ‚ ÓÚ΢ˠÓÚ Â‡ÍˆËË ÓÚÚÓÊÂÌËfl Ú‡ÌÒÔ·ÌÚ‡ÌÚ‡ ËÎË ÏÌÓ„Ëı ‰Û„Ëı ËÏÏÛÌÌ˚ı ‡͈ËÈ, ÍÓÚÓ˚ ÔÓÚÂ͇˛Ú ‚ Ú˜ÂÌË ÌÂÒÍÓθÍËı ˜‡ÒÓ‚ ËÎË ÌÂÒÍÓθÍËı ‰ÌÂÈ [35]. ä‡ÈÌ ‚‡ÊÌÓÈ fl‚ÎflÂÚÒfl ÔÓ·ÎÂχ ̇ۯÂÌËfl „ÛÎflˆËË ËÏÏÛÌÌÓ„Ó ÓÚ‚ÂÚ‡ ‚ ÓÚÌÓ¯ÂÌËË ÒÓ·ÒÚ‚ÂÌÌ˚ı ÍÎÂÚÓÍ (β-ÍÎÂÚÓÍ), Ú. Í. ËÏÏÛÌ̇fl ÒËÒÚÂχ Ó͇Á˚‚‡ÂÚ ‚ÎËflÌË ̇ ÔÓˆÂÒÒ Á‡·Ó΂‡ÌËfl Á‡‰ÓÎ„Ó ‰Ó ÔÓfl‚ÎÂÌËfl ÍÎËÌ˘ÂÒÍËı ÒËÏÔÚÓÏÓ‚ Ò‡ı‡ÌÓ„Ó ‰Ë‡·ÂÚ‡. èÓÒΉÌË ËÒÒΉӂ‡ÌËfl „Ó‚ÓflÚ Ó ÚÓÏ, ˜ÚÓ Ì‡Û¯ÂÌËfl ÌÓχθÌÓÈ Â„ÛÎflˆËË ‡ÛÚÓ‡ÍÚË‚ÌÓ„Ó Ë ‡ÛÚÓÔÓÚÂÍÚË‚ÌÓ„Ó ËÏÏÛÌÌÓ„Ó ÓÚ‚ÂÚ‡ ÏÓ„ÛÚ fl‚ÎflÚ¸Òfl ÂÁÛθڇÚÓÏ ÌÂÔ‡‚ËθÌÓ„Ó ÙÛÌ͈ËÓÌËÓ‚‡ÌËfl ÔÓÔÛÎflˆËË í-ÍÎÂÚÓÍ, ÍÓÚÓ˚ ‡ÒÔÓÁ̇˛ÚÒfl ÔÓ ˝ÍÒÔÂÒÒËË ÏÓÎÂÍÛÎ˚ ëÑ25 [27]. ë Û˜ÂÚÓÏ ÌÓ‚˚ı ‰‡ÌÌ˚ı å. Atkinson Ë G. Eisenbarth ÓÔÛ·ÎËÍÓ‚‡ÎË ÒÓ‚ÂÏÂÌÌÛ˛ ÚÂÓ˲ Ô‡ÚÓ„ÂÌÂÁ‡ ëÑ 1 ÚËÔ‡ [7,4] (ËÒ. 2). ÇÏÂÒÚÓ „ÂÌÂÚ˘ÂÒÍÓÈ Ô‰‡ÒÔÓÎÓÊÂÌÌÓÒÚË ‚ ÌÂÈ ÓÚϘ‡ÂÚÒfl ‚Á‡ËÏÓ‰ÂÈÒÚ‚Ë ÏÂÊ‰Û „Â̇ÏË, ÒÔÓÒÓ·ÒÚ‚Û˛˘ËÏË Ë ÔÂÔflÚÒÚ‚Û˛˘ËÏË ‡Á‚ËÚ˲ ëÑ 1 ÚËÔ‡. äÓÏ ÚÓ„Ó, ‡ÒÒχÚË‚‡ÂÚÒfl Ù‡ÍÚ, ˜ÚÓ ˝ÚË „ÂÌ˚ Ù‡ÍÚ˘ÂÒÍË ‚ÎËfl˛Ú ̇ ‚ÓÒÔËËϘ˂ÓÒÚ¸ Ë ÒÓÔÓÚË‚ÎflÂÏÓÒÚ¸ Í CÑ 1 ÚËÔ‡ ‚ ıӉ ‚ÒÂ„Ó ÔÂËÓ‰‡, Ô‰¯ÂÒÚ‚Û˛˘Â„Ó Á‡·Ó΂‡Ì˲ ‰Ë‡·ÂÚÓÏ, ‡ Ì ÚÓθÍÓ ‚ ÔÂËÓ‰, Ô‰¯ÂÒÚ‚Û˛˘ËÈ ‡ÛÚÓËÏÏÛÌÌÓÈ Ë̉Û͈ËË. èË ÓˆÂÌÍ ‚ÎËflÌËfl Ù‡ÍÚÓÓ‚ ÓÍÛʇ˛˘ÂÈ Ò‰˚ ̇ ‡Á‚ËÚË ҇ı‡ÌÓ„Ó ‰Ë‡·ÂÚ‡ 1 ÚËÔ‡ ‡ÒÒχÚË‚‡˛ÚÒfl ‡Á΢Ì˚ ÔËÓ‰Ì˚ ÔÓˆÂÒÒ˚, Ó͇Á˚‚‡˛˘Ë ‚ÓÁ‰ÂÈÒÚ‚Ë ̇ Ú˜ÂÌË ‰Ë‡·ÂÚ‡ Á‡ ‚ÂÒ¸ ÔÂËÓ‰ Á‡·Ó΂‡ÌËfl, ‚Íβ˜‡fl Ë Â„Ó ‰ÓÍÎËÌ˘ÂÒÍÛ˛ ÒÚ‡‰Ë˛, ‡ Ì ÚÓθ- ÍÓ Ù‡ÍÚÓ, ÔÓ‚ÓˆËÛ˛˘ËÈ ÍÎËÌ˘ÂÒÍËÈ ‰Â·˛Ú Á‡·Ó΂‡ÌËfl, ̇ÔËÏ ‚ËÛÒ̇fl ËÌÙÂ͈Ëfl. ÑÛ„ËÏ ‡ÒÔÂÍÚÓÏ, ÍÓÚÓ˚È ÌÂÓ·ıÓ‰ËÏÓ ÔÂÂÒÏÓÚÂÚ¸, fl‚ÎflÂÚÒfl ÙÂÌÓÏÂÌ ÔÓÚÂË β-ÍÎÂÚÓÍ; ÂÒÚ¸ ‚ÂÓflÚÌÓÒÚ¸ ÚÓ„Ó, ˜ÚÓ Â ‚˚‡ÊÂÌÌÓÒÚ¸ ·Û‰ÂÚ ÒÛ˘ÂÒÚ‚ÂÌÌÓ ËÁÏÂÌflÚ¸Òfl ‚ Á‡‚ËÒËÏÓÒÚË ÓÚ ÚËÔ‡ ËÌÒÛÎËÚ‡, ÒÚÂÔÂÌË „Ë·ÂÎË β-ÍÎÂÚÓÍ Ë Ëı ÒÔÓÒÓ·ÌÓÒÚË Í Â„Â̇ˆËË [22]. Ç Ì‡ÒÚÓfl˘Â ‚ÂÏfl ‰Ó ÍÓ̈‡ ÌÂflÒÌ˚Ï ÓÒÚ‡ÂÚÒfl ÏÂı‡ÌËÁÏ ‡ÛÚÓËÏÏÛÌÌÓÈ Â‡ÍˆËË, Ô‰‚‡fl˛˘ÂÈ ‡ÒÔ‡‰ β-ÍÎÂÚÓÍ, ‚ ÓÒÓ·ÂÌÌÓÒÚË Â‡ÍˆËfl β-ÍÎÂÚÍË Ì‡ ‡ÛÚÓËÏÏÛÌÌ˚ ‡ÌÚËÚ· [36]. àÒıÓ‰fl ËÁ ÒÓ‚ÂÏÂÌÌ˚ı Ô‰ÒÚ‡‚ÎÂÌËÈ Ó Ô‡ÚÓ„ÂÌÂÁ ëÑ 1 ÚËÔ‡, „Ë·Âθ β-ÍÎÂÚÓÍ ÏÓÊÂÚ ÔÓËÒıÓ‰ËÚ¸ ‚ ÂÁÛθڇÚ ‡ÁÌ˚ı Ô‡ÚÓÎӄ˘ÂÒÍËı ÔÓˆÂÒÒÓ‚. é‰ËÌ ËÁ ÌËı – ‰ÂÒÚÛ͈Ëfl ËÎË ÌÂÍÓÁ β-ÍÎÂÚÓÍ, ‰Û„ÓÈ – ‡ÔÓÔÚÓÁ ËÎË „ÂÌÂÚ˘ÂÒÍË Á‡ÔÓ„‡ÏÏËÓ‚‡ÌÌ˚È ÔÓˆÂÒÒ „Ë·ÂÎË ÍÎÂÚÓÍ. çÂÍÓÁ – ˝ÚÓ Ô‡ÚÓÎӄ˘ÂÒÍËÈ ÔÓˆÂÒÒ, ‡Á‚Ë‚‡˛˘ËÈÒfl Ó‰ÌÓ‚ÂÏÂÌÌÓ ‚ ·Óθ¯ÓÈ „ÛÔÔ ÍÎÂÚÓÍ ‚ ÂÁÛθڇÚ „ËÔÓÍÒËË, ÙËÁ˘ÂÒÍËı Ë ÚÓÍÒ˘ÂÒÍËı ‚ÓÁ‰ÂÈÒÚ‚ËÈ, ÔÓ‰ ‰ÂÈÒÚ‚ËÂÏ ÍÓÏÔÎÂÏÂÌÚ‡ ËÎË ‚ËÛÒ‡. çÂÍÓÁ ÒÓÔÓ‚Óʉ‡ÂÚÒfl ÓÚÂÍÓÏ ÍÎÂÚÍË, ‡ÌÌÂÈ ÔÓÚÂÂÈ ˆÂÎÓÒÚÌÓÒÚË Â ÏÂÏ·‡Ì˚, ÔÓ‚ÂʉÂÌËÂÏ ÏËÚÓıÓ̉ËÈ Ë ‰Û„Ëı Ó„‡ÌÂÎÎ, ˜ÚÓ ‚ ÍÓ̘ÌÓÏ Ò˜ÂÚ Á‡Í‡Ì˜Ë‚‡ÂÚÒfl ÎËÁËÒÓÏ ÓÒÚ‡ÚÍÓ‚ ÍÎÂÚÍË [1]. çÂÍÓÁ ÍÎÂÚÍË ÒÚ‡ÌÓ‚ËÚÒfl Ô˘ËÌÓÈ ÔÓ‚ÂʉÂÌËfl Ë ‚ÓÒÔ‡ÎÂÌËfl ÓÍÛʇ˛˘Ëı ÍÎÂÚÓÍ Ë ‚ˉÂÌ Ì‡ ÒÂÁ Ú͇ÌÂÈ. β-äÎÂÚÍË ÔÓ‰‚„‡˛ÚÒfl ÌÂÍÓÁÛ ‚ ÔËÒÛÚÒÚ‚ËË ËÁ·˚ÚÓ˜ÌÓ„Ó ÍÓ΢ÂÒÚ‚‡ Ò‚Ó·Ó‰Ì˚ı ‡‰Ë͇ÎÓ‚ – ÍËÒÎÓÓ‰Ì˚ı ‡‰Ë͇ÎÓ‚ ËÎË ÓÍÒˉ‡ ‡ÁÓÚ‡ ËÎË ÔÓ‰ 3/2006 61 Обзоры литературы Сахарный диабет ИЛ-1 ФНОα ИФНγ CD4+ T-клетки Макрофаг ИЛ-2 ИЛ-1 ФНОα ИФНγ Fas-L Цитотоксические Т-клетки Fas Активация каспазного пути ИЛ-1 ФНОα ИФНγ Перфорин Свободные радикалы кислорода NO Гранзим В ФНОα β−клетка ИЛ-1 ФНОα ИФНγ Рис. 3. Механизм деструкции β-клетки при сахарном диабете типа 1. E. Kawasaki et al. / diabetes Research and Clinical Practice 66 (2004) S27-S32. ‰ÂÈÒÚ‚ËÂÏ ÔÓ‚ÓÒÔ‡ÎËÚÂθÌ˚ı ˆËÚÓÍËÌÓ‚. çÂÍÓÁ Ì ҂flÁ‡Ì Ò ÔÓÚ·ÎÂÌËÂÏ ˝Ì„ËË Ë ÒËÌÚÂÁÓÏ ·ÂÎ͇, ÚÓ„‰‡ Í‡Í ‡ÔÓÔÚÓÁ – ˝ÚÓ ˝Ì„ÓÁ‡‚ËÒËÏ˚È ÔÓˆÂÒÒ. íÂÏËÌ «‡ÔÓÔÚÓÁ» ÒÓÓÚ‚ÂÚÒÚ‚ÛÂÚ ÛÒÒÍÓÏÛ «ÎËÒÚÓÔ‡‰», ‚ ÔÓˆÂÒÒ ‡ÔÓÔÚÓÁ‡ ÍÎÂÚ͇ ËÒ˜ÂÁ‡ÂÚ ‚ Ú˜ÂÌË 15–120 ÏËÌ. Ç ·Óθ¯ËÌÒÚ‚Â ÒÎÛ˜‡Â‚ ‡ÔÓÔÚÓÁ Ò‚flÁ‡Ì Ò ‡ÍÚË‚‡ˆËÂÈ ÒÔˆËÙ˘ÂÒÍËı ˆËÒÚÂËÌÓ‚˚ı ÔÓÚ‡Á – ͇ÒÔ‡Á, ÒÛ˘ÂÒÚ‚Û˛˘Ëı ‚ ÍÎÂÚÍ ‚ ‚ˉ Ì‡ÍÚË‚Ì˚ı ÙÓÏ – ÔÓ͇ÒÔ‡Á. Ç Ì‡Á‚‡ÌËË «Caspase» ÓÚ‡ÊÂÌ ÏÂı‡ÌËÁÏ ÔÓÚÂÓÎËÁ‡: ‚ ‡ÍÚË‚ÌÓÏ ˆÂÌÚ ̇ıÓ‰ËÚÒfl ˆËÒÚÂËÌ, ‡ÒÔ‡‡„ËÌÓ‚‡fl ÍËÒÎÓÚ‡ ‡ÒÔÓÁ̇ÂÚÒfl Í‡Í ÒÛ·ÒÚ‡Ú. ä‡ÒÔ‡Á˚ ‡Ò˘ÂÔÎfl˛Ú ·ÂÎÍË ÔÓÒΠÓÒÚ‡ÚÍÓ‚ ‡ÒÔ‡‡„ËÌÓ‚ÓÈ ÍËÒÎÓÚ˚. Ç ÂÁÛθڇÚ ‰ÂÈÒÚ‚Ëfl ͇ÒÔ‡Á ÔÓËÒıÓ‰ËÚ ‡ÁÛ¯ÂÌË ·ÂÎÍÓ‚, Û˜‡ÒÚ‚Û˛˘Ëı ‚ ÙÓÏËÓ‚‡ÌËË ˆËÚÓÒÍÂÎÂÚ‡; „ˉÓÎËÁ ·ÂÎÍÓ‚ fl‰ÂÌÓÈ ÏÂÏ·‡Ì˚, ÍÓ̉ÂÌÒ‡ˆËfl ıÓχÚË̇; ‡Ò˘ÂÔÎÂÌË ‡ÌÚˇÔÓÔÚÓÁÌ˚ı ·ÂÎÍÓ‚ ÒÂÏÂÈÒÚ‚‡ ÇÒl-2; ÔÓÚÂÓÎËÁ ËÌ„Ë·ËÚÓ‡ Ñçä-‡Á˚, ÓÚ‚ÂÚÒÚ‚ÂÌÌÓ„Ó Á‡ Ù‡„ÏÂÌÚ‡ˆË˛ Ñçä; Ë̇ÍÚË‚‡ˆËfl Ë Ì‡Û¯ÂÌË „ÛÎflˆËË ·ÂÎÍÓ‚, Û˜‡ÒÚ‚Û˛˘Ëı ‚ ÂÔ‡‡ˆËË Ñçä (Ï˯Â̸˛ ͇ÒÔ‡Á fl‚ÎflÂÚÒfl ÔÓÎË(ÄÑê-Ë·ÓÔÓÎËχÁ‡). ëÛ˘ÂÒÚ‚ÛÂÚ ÌÂÒÍÓθÍÓ ÔÛÚÂÈ Â‡ÎËÁ‡ˆËË ÔÓ„‡ÏÏ˚ ÍÎÂÚÓ˜ÌÓÈ ÒÏÂÚË: Ò Û˜‡ÒÚËÂÏ ÂˆÂÔÚÓÓ‚ Ô·ÁχÚ˘ÂÒÍÓÈ ÏÂÏ·‡Ì˚; Ò Û˜‡ÒÚËÂÏ ÏËÚÓıÓ̉ˇθÌÓ„Ó ˆËÚÓıÓχ ë. êˆÂÔÚÓ, Ó·ÓÁ̇˜‡ÂÏ˚È Fas (Apo-1 CD-95), ‚Á‡ËÏÓ‰ÂÈÒÚ‚Ûfl Ò ÒÓÓÚ‚ÂÚÒÚ‚Û˛˘ËÏ ÎË„‡Ì‰ÓÏ (Fas-l) Ú‡ÌÒÏÂÏ·‡ÌÌ˚Ï ·ÂÎÍÓÏ í-ÍËη, ‡ÍÚË‚ËÛÂÚÒfl Ë Á‡ÔÛÒ͇ÂÚ ÔÓ„‡ÏÏÛ „Ë·ÂÎË ÍÎÂÚÍË [16]. èË ‡ÍÚË‚‡ˆËË Í‡ÒÔ‡Á˚ ÔÂ‚Ó„Ó ˝¯ÂÎÓ̇ ÊËÁ̸ ÍÎÂÚÍË Â˘Â ÏÓÊÌÓ ÒÓı‡ÌËÚ¸. ëÛ˘ÂÒÚ‚Û˛Ú Â„ÛÎflÚÓ- 62 3/2006 ˚, ÍÓÚÓ˚ ·ÎÓÍËÛ˛Ú ËÎË Ì‡Ó·ÓÓÚ ÛÒËÎË‚‡˛Ú ‡ÁÛ¯ËÚÂθÌÓ ‰ÂÈÒÚ‚Ë ͇ÒÔ‡Á ÔÂ‚Ó„Ó ˝¯ÂÎÓ̇. èË ‡ÍÚË‚‡ˆËË Í‡ÒÔ‡Á ‚ÚÓÓ„Ó ˝¯ÂÎÓ̇ (˝ÙÙÂÍÚÓÌ˚ı ͇ÒÔ‡Á) ÔÓˆÂÒÒ, Á‡ÔÛ˘ÂÌÌ˚È ÔÓ„‡ÏÏÓÈ ÒÏÂÚË, Ó͇Á˚‚‡ÂÚÒfl ÌÂÓ·‡ÚËÏ˚Ï. ÑÛ„ÓÈ ÔÛÚ¸ ‡ÎËÁ‡ˆËË ÔÓ„‡ÏÏ˚ ‡ÔÓÔÚÓÁ‡ Á‡‚ËÒËÚ ÓÚ ÏËÚÓıÓ̉ˇθÌÓ„Ó ˆËÚÓıÓχ ë. èË ÔÓ‚ÂʉÂÌËË ÏËÚÓıÓ̉ËÈ, ̇ÔËÏ ÔË ËÒÚÓ˘ÂÌËË ÍÎÂÚÓÍ, ‚ÓÒÒÚ‡ÌÓ‚ÎÂÌÌ˚Ï „βڇÚËÓÌÓÏ ËÎË çÄÑîç, ÔÓËÒıÓ‰ËÚ Ó·‡ÁÓ‚‡ÌË „Ë„‡ÌÚÒÍÓÈ ÔÓ˚ ËÎË „Ë„‡ÌÚÒÍÓ„Ó ·ÂÎÍÓ‚Ó„Ó Í‡Ì‡Î‡ ‚ Ò‡ÏÓÈ Ì‡ÛÊÌÓÈ ÏÂÏ·‡ÌÂ Ë ‚˚Ò‚Ó·ÓʉÂÌË ‡ÒÚ‚ÓËÏ˚ı ·ÂÎÍÓ‚ ÏÂÊÏÂÏ·‡ÌÌÓ„Ó ÔÓÒÚ‡ÌÒÚ‚‡, ÒÂ‰Ë ÌËı – ‡ÔÓÔÚÓ„ÂÌÌ˚ هÍÚÓ˚, ˆËÚÓıÓÏ ë Ë ÔÓ͇ÒÔ‡Á˚. á‡ÚÂÏ Á‡ÔÛÒ͇ÂÚÒfl ͇Ò͇‰ ͇ÒÔ‡Á, ‚Â‰Û˘ËÈ Í „Ë·ÂÎË ÍÎÂÚÍË. ê‡Á΢Ì˚ ÔÛÚË ‡ÔÓÔÚÓÁ‡ ÏÓ„ÛÚ ‚Á‡ËÏÓ‰ÂÈÒÚ‚Ó‚‡Ú¸ ÏÂÊ‰Û ÒÓ·ÓÈ. èÓ„‡ÏÏËÛÂχfl ÍÎÂÚӘ̇fl ÒÏÂÚ¸ ÏÓÊÂÚ ·˚Ú¸ ‡ÎËÁÓ‚‡Ì‡ ‚ ÂÁÛθڇÚ ÍÓÏ·ËÌËÓ‚‡ÌÌÓ„Ó ‰ÂÈÒÚ‚Ëfl ‰‚Ûı ÔÛÚÂÈ – Ò Û˜‡ÒÚËÂÏ Ë ÂˆÂÔÚÓÓ‚ Ô·ÁχÚ˘ÂÒÍÓÈ ÏÂÏ·‡Ì˚ Ë ÏËÚÓıÓ̉ˇθÌÓ„Ó ˆËÚÓıÓχ ë. Ç ÔÓÒΉÌË „Ó‰˚ ·˚ÎÓ ÔÓ͇Á‡ÌÓ, ˜ÚÓ ÔÓˆÂÒÒ˚ ÌÂÍÓÁ‡ Ë ‡ÔÓÔÚÓÁ‡ Ì ÔÓÚË‚ÓÒÚÓflÚ ‰Û„ ‰Û„Û. LJÊÌÛ˛ Óθ ‚ ÔÓˆÂÒÒ ÍÎÂÚÓ˜ÌÓÈ „Ë·ÂÎË Ë„‡˛Ú ˆËÚÓÍËÌ˚ – ÒÂÍÂÚÓÌ˚ ·ÂÎÍË, ‚˚ÔÓÎÌfl˛˘Ë ÙÛÌÍˆË˛ ωˇÚÓÓ‚ ÏÂÊÍÎÂÚÓ˜Ì˚ı Ò˄̇ÎÓ‚ Ë ÓÒÌÓ‚Ì˚ı „ÛÎflÚÓÓ‚ ‡ÍÚË‚ÌÓÒÚË ËÏÏÛÌÌÓÈ ÒËÒÚÂÏ˚. ñËÚÓÍËÌ˚ ̇Á˚‚‡˛Ú «·ÂÎ͇ÏË Ò‚flÁË». Ç Á‡‚ËÒËÏÓÒÚË ÓÚ Ó·ÂÒÔ˜ÂÌËfl ÍÎÂÚÓ˜Ì˚ı ËÎË „ÛÏӇθÌ˚ı ÙÓÏ ËÏÏÛÌÌÓ„Ó ÓÚ‚ÂÚ‡ ˆËÚÓÍËÌ˚ ÏÓ„ÛÚ ·˚Ú¸ ÓÚÌÂÒÂÌ˚ Í Th1 ËÎË Í Th2 ıÂÎÔÂÌ˚Ï ÍÎÂÚ͇Ï. ä Th-1 ÓÚÌÓÒflÚÒfl àã-2,3,àçîγ, îçéα,îçéβ. ä Th-2 ÓÚ- Обзоры литературы Более эффективные методы по предотвращению заболевания Сахарный диабет Высокая точность предсказания заболевания Масса β-клеток Способность предсказать CД 1 типа Низкая точность предсказания заболевания Менее эффективные методы по предотвращению заболевания Рис. 4. «Дилемма лечения». ÌÓÒflÚÒfl àã-4,5,6,9,10,13. çÂÍÓÚÓ˚ ˆËÚÓÍËÌ˚ ÏÓ„ÛÚ ‡ÍÚË‚ËÓ‚‡Ú¸ ÏÂı‡ÌËÁÏ Ò˄̇ÎËÁ‡ˆËË, ‚Â‰Û˘ËÈ Í „Ë·ÂÎË ÍÎÂÚÍË (ËÒ. 3) [26]. Ç ·Óθ¯ËÌÒÚ‚Â ËÒÒΉӂ‡ÌËÈ, ÔÓÒ‚fl˘ÂÌÌ˚ı ëÑ 1 ÚËÔ‡, ̇ԇ‚ÎÂÌÌ˚ı ̇ ËÁÛ˜ÂÌË ̇ۯÂÌËÈ ÙÛÌ͈ËÈ ËÏÏÛÌÌÓÈ ÒËÒÚÂÏ˚, ËÒÔÓθÁÓ‚‡Î‡Ò¸ ‚ ͇˜ÂÒڂ χÚ¡· ÍÓ‚¸ ËÁ ÔÂËÙ¢ÂÒÍËı ‚ÂÌ, ‚ ÚÓ ‚ÂÏfl Í‡Í Ó˜‡„ÓÏ ıÓÌ˘ÂÒÍÓ„Ó ‚ÓÒÔ‡ÎÂÌËfl ÔË ‰Ë‡·ÂÚ fl‚ÎflÂÚÒfl ÔÓ‰ÊÂÎۉӘ̇fl ÊÂÎÂÁ‡. é˜Â‚ˉÌÓ, ˜ÚÓ ÔӉӷ̇fl ‡ÁÌˈ‡ ÔË ËÒÒΉӂ‡ÌËË Ï‡Ú¡· ‚˚Á˚‚‡ÂÚ ÌÂχÎÓ ÍÓ΢ÂÒÚ‚Ó Ó¯Ë·ÓÍ Ë ‡ÚÂÙ‡ÍÚÓ‚ [10,6]. Ç ıӉ ԇÍÚ˘ÂÒÍËı ËÒÒΉӂ‡ÌËÈ, ÔÓÒ‚fl˘ÂÌÌ˚ı ÔÓÙË·ÍÚËÍ Á‡·Ó΂‡ÂÏÓÒÚË, ÒÛ˘ÂÒÚ‚ÛÂÚ ÏÌÓ„Ó ÔÂÔflÚÒÚ‚ËÈ. ëÂ‰Ë ÌËı ˝Ú˘ÂÒÍË ‡ÒÔÂÍÚ˚, ‚Íβ˜‡˛˘Ë Ê·ÌË ԇˆËÂÌÚÓ‚ Á̇ڸ Ó ‡Á‚ËÚËË Á‡·Ó΂‡ÌËfl ‚ ·Û‰Û˘ÂÏ, ‚ÓÁÏÓÊÌÓÒÚ¸ Ôӂ‰ÂÌËfl Ú‡ÍÓ„Ó Ó‰‡ ÒÍËÌËÌ„‡ ÔË ÓÚÒÛÚÒÚ‚ËË ÏÂÚÓ‰Ó‚ Ô‰ÛÔÂʉÂÌËfl Á‡·Ó΂‡ÂÏÓÒÚË ëÑ 1 ÚËÔ‡, ̇ۯÂÌË ÍÓÌÙˉÂ̈ˇθÌÓÒÚË, ‚ÓÔÓÒ˚ Ó„‡ÌËÁ‡ˆËË Ô‡ÍÚ˘ÂÒÍÓ„Ó ÓÒÛ˘ÂÒÚ‚ÎÂÌËfl ÒÍËÌËÌ„‡ Ë, ÍÓ̘ÌÓ, ÙË̇ÌÒÓ‚˚ ·‡¸Â˚ [20]. è‚Ó̇˜‡Î¸Ì˚È ÓÔÚËÏËÁÏ ËÒÒΉӂ‡ÚÂÎÂÈ, ͇҇˛˘ËÈÒfl ˉÂÌÚËÙË͇ˆËË ÏÂÚÓ‰‡ Ô‰ÛÔÂʉÂÌËfl Á‡·Ó΂‡ÂÏÓÒÚË ëÑ 1 ÚËÔ‡ ÔË ËÒÔÓθÁÓ‚‡ÌËË ÊË‚ÓÚÌ˚ı ÏÓ‰ÂÎÂÈ, ÔË‚ÂÎ Í‡Í Í ÓÚÍ˚ÚËflÏ, Ú‡Í Ë Í ‡ÁÓ˜‡Ó‚‡ÌËflÏ ‚ ÓÚÌÓ¯ÂÌËË ÔËÏÂÌÂÌËfl ‡Ì‡Îӄ˘Ì˚ı ÏÂÚÓ‰Ó‚ Û ˜ÂÎÓ‚Â͇. Ç 1994 „. ÓÔÛ·ÎËÍÓ‚‡ÌÓ 70 ÏÂÚÓ‰Ó‚, ÍÓÚÓ˚ ÏÓ„ÛÚ ·˚Ú¸ ËÒÔÓθÁÓ‚‡Ì˚ ‰Îfl Ô‰ÛÔÂʉÂÌËfl Á‡·Ó΂‡ÂÏÓÒÚË ëÑ 1 ÚËÔ‡ NOD Ï˚¯ÂÈ [13], ‚ 1998 „. Ëı ·˚ÎÓ ÛÊ 125 [9], ‚ 2004 „. ÓÔËÒ‡ÌÓ ÛÊ 192 ÏÂÚÓ‰‡ [37]. ä‡ÍÓ‚˚ Ô˘ËÌ˚ ÚÓ„Ó, ˜ÚÓ ÔÓˆÂÒÒ Ô‰ÛÔÂʉÂÌËfl Способность предотвратить CД1 типа Начало клинически явного СД 1 типа Á‡·Ó΂‡ÂÏÓÒÚË ‰Ë‡·ÂÚÓÏ Û Ï˚¯ÂÈ Ó͇Á˚‚‡ÂÚÒfl ÓÚÌÓÒËÚÂθÌÓ ÔÓÒÚ˚Ï, ‡ Û Î˛‰ÂÈ ˜ÂÁ‚˚˜‡ÈÌÓ ÒÎÓÊÌ˚Ï? é‰ÌÓÈ ËÁ Ô˘ËÌ ÏÓÊÂÚ fl‚ÎflÚ¸Òfl ÚÓ, ˜ÚÓ ·Óθ¯Â Á̇˜ÂÌË Ôˉ‡ÂÚÒfl ÒıÓ‰ÒÚ‚Û Á‡·Ó΂‡ÌËÈ ëÑ 1 ÚËÔ‡ Û NOD Ï˚¯ÂÈ Ë ˜ÂÎÓ‚Â͇, ˜ÂÏ Ëı ‡ÁÎË˜Ë˛ [38]. Ç ‰ÂÈÒÚ‚ËÚÂθÌÓÒÚË Ó·‡ ‰Ë‡·ÂÚ‡ (Ï˚¯ËÌ˚È Ë ˜ÂÎӂ˜ÂÒÍËÈ) ËÏÂ˛Ú ÔÓÎË„ÂÌÌÛ˛ ˝ÚËÓÎӄ˲, ı‡‡ÍÚÂËÁÛ˛ÚÒfl ̇ۯÂÌËflÏË ‚ „ÛÎflˆËË ËÏÏÛÌÌÓ„Ó ÓÚ‚ÂÚ‡ Ë ÒÔÓÒÓ·ÌÓÒÚ¸˛ Í ÂÏËÒÒËË Á‡·Ó΂‡ÌËfl ÔÓÒΠڇÌÒÔ·ÌÚ‡ˆËË ÍÓÒÚÌÓ„Ó ÏÓÁ„‡. íÂÏ Ì ÏÂÌÂÂ, ËÏÂÂÚÒfl Ë fl‰ ÒÛ˘ÂÒÚ‚ÂÌÌ˚ı ÓÚ΢ËÈ [28]: ÔÓ͇Á‡ÌÓ ‡Á΢ÌÓ ‰ÂÈÒÚ‚Ë χÚÂËÌÒÍËı ‡ÛÚÓ‡ÌÚËÚÂÎ Û Ï˚¯Ë Ë Û ˜ÂÎÓ‚Â͇; ‡Á΢Ëfl ̇·Î˛‰‡˛ÚÒfl Ë ‚ ˜‡ÒÚÓÚ Á‡·Ó΂‡ÂÏÓÒÚË Ë ÔÓÎÓ‚ÓÈ ÔË̇‰ÎÂÊÌÓÒÚË; ËÌÒÛÎËÚ Û NOD-Ï˚¯ÂÈ ÔÓÚÂ͇ÂÚ ‚ ΄ÍÓÈ ÙÓÏÂ, ‰Ó·Ó͇˜ÂÒÚ‚ÂÌÌÓ. ç‡ÍÓ̈, ÙÛÌ͈ËÓÌËÓ‚‡ÌË ËÏÏÛÌÌ˚ı ÒËÒÚÂÏ Ï˚¯Ë Ë ˜ÂÎÓ‚Â͇ ËÏÂÂÚ Á̇˜ËÚÂθÌ˚ ‡Á΢Ëfl [31]. Ç 2005 „. M. A. Atkinson Ë D. Schatz ÓÔÛ·ÎËÍÓ‚‡ÎË ÒıÂÏÛ, ̇Á‚‡ÌÌÛ˛ «‰ËÎÂÏÏÓÈ Î˜ÂÌËfl», ‚ ÍÓÚÓÓÈ ÒÔÓÒÓ·ÌÓÒÚ¸ Ô‰Ò͇Á˚‚‡Ú¸ ëÑ 1 ÚËÔ‡ Ë ÒÔÓÒÓ·ÌÓÒÚ¸ Ô‰ÓÚ‚‡˘‡Ú¸ ˝ÚÓ Á‡·Ó΂‡ÌË Ô‰ÒÚ‡‚ÎÂÌ˚ ‰‚ÛÏfl ÎËÌËflÏË, ̇ԇ‚ÎÂÌÌ˚ÏË ‚ ÔÓÚË‚ÓÔÓÎÓÊÌ˚ ÒÚÓÓÌ˚ [4] (ËÒ. 4). ç‡ ‡ÌÌËı ÒÚ‡‰Ëflı ÔÓˆÂÒÒ‡ ÚÓ˜ÌÓÒÚ¸ Ô‰Ò͇Á‡ÌËfl ÌËÊÂ, ˜ÂÏ ‚ ÔÂËÓ‰, ÍÓ„‰‡ ÔÓfl‚Îfl˛ÚÒfl Ô‚˚ ÒËÏÔÚÓÏ˚ ‰Ë‡·ÂÚ‡, ÌÓ ˜ÂÏ ‡Ì¸¯Â ̇˜‡ÚÓ Î˜ÂÌË ÔÂÔ‡‡Ú‡ÏË, ‚ÓÁ‰ÂÈÒÚ‚Û˛˘ËÏË Ì‡ „ÛÎflˆË˛ ËÏÏÛÌÌÓ„Ó ÓÚ‚ÂÚ‡, ÚÂÏ ‚˚¯Â ·Û‰ÂÚ Â„Ó ˝ÙÙÂÍÚË‚ÌÓÒÚ¸. çÂÔÓÒ‰ÒÚ‚ÂÌÌÓ ‚ ̇˜‡Î ÍÎËÌ˘ÂÒÍÓ„Ó ‰Â·˛Ú‡ ëÑ 1 ÚËÔ‡ ڇ͇fl Ú‡ÔËfl ÏÂÌ ˝ÙÙÂÍÚ˂̇. èË Ôӂ‰ÂÌËË Ú‡ÔËË 3/2006 63 Обзоры литературы Сахарный диабет ‰Ó ÍÎËÌ˘ÂÒÍÓ„Ó Ì‡˜‡Î‡ Á‡·Ó΂‡ÌËfl ÒÚ‡ÌÂÚ ‚ÓÁÏÓÊÌ˚Ï ‡Á‡·ÓÚ‡Ú¸ ·ÓΠ˝ÙÙÂÍÚË‚Ì˚ ÏÂÚÓ‰˚ ΘÂÌËfl. ëÓÓÍ ÎÂÚ Ì‡Á‡‰ ·˚ÎÓ ÓÚϘÂÌÓ, ˜ÚÓ ‚ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ ·ÓθÌ˚ı Ò Ì‰‡‚ÌÓ ‰Ë‡„ÌÓÒÚˆËÓ‚‡ÌÌ˚Ï ëÑ 1 ÚËÔ‡ ÓÒÚÓ‚ÍÓ‚˚ ÍÎÂÚÍË Ì‡˜Ë̇˛Ú ÓÚÒÓ‰ËÌflÚ¸Òfl ÓÚ Ô‡Ì͇ڢÂÒÍËı ÔÓÚÓÍÓ‚. äÓÏ ÚÓ„Ó, β-ÍÎÂÚÍË, ÒÔÓÒÓ·Ì˚ ÒÂÍÂÚËÓ‚‡Ú¸ ËÌÒÛÎËÌ, ·˚ÎË ‚˚fl‚ÎÂÌ˚ ‚ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ ·ÓθÌ˚ı, ÍÓÚÓ˚ ÒÚ‡‰‡ÎË ëÑ 1 ÚËÔ‡ ‰‡Ê ‰ÎËÚÂθÌÓ ‚Â- Ïfl. é˜Â‚ˉÌÓ, ˜ÚÓ ÒÛ˘ÂÒÚ‚ÛÂÚ ÔÓÚÂ̈ˇΠ˝Ì‰Ó„ÂÌÌÓ-„Â̇ÚË‚ÌÓÈ ÒÔÓÒÓ·ÌÓÒÚË β-ÍÎÂÚÓÍ. 燘‡ÎÓ „ËÔ„ÎËÍÂÏËË ‰ÂÈÒÚ‚ËÚÂθÌÓ ÏÓÊÂÚ ‡ÒÒÓˆËËÓ‚‡Ú¸Òfl Ò ·Óθ¯ÂÈ ÓÒÚÓ‚ÍÓ‚ÓÈ ÍÎÂÚÓ˜ÌÓÈ Ï‡ÒÒÓÈ, ˜ÂÏ ÔÓ·„‡ÎË ‡ÌÂÂ. èÂÒÔÂÍÚË‚Ì˚Ï Ô‰ÒÚ‡‚ÎflÂÚÒfl ËÁÛ˜ÂÌË ÒÔÓÒÓ·ÌÓÒÚË β-ÍÎÂÚÓÍ Í Â„Â̇ˆËË Ë ‡ÒÒÏÓÚÂÌË ÏÓ‰ÂÎË Â„Â̇ˆËË ÓÒÚÓ‚ÍÓ‚˚ı ÍÎÂÚÓÍ Û ·ÓθÌ˚ı Ò ‚Ô‚˚ ‚˚fl‚ÎÂÌÌ˚Ï ëÑ 1 ÚËÔ‡. 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