Современные аспекты патогенеза сахарного диабета 1 типа

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Обзоры литературы
Современные аспекты патогенеза
сахарного диабета 1 типа
í.Ç. çËÍÓÌÓ‚‡
Éì ù̉ÓÍËÌÓÎӄ˘ÂÒÍËÈ Ì‡Û˜Ì˚È ˆÂÌÚ
(‰Ë. – ‡Í‡‰. êÄç Ë êÄåç à.à. щӂ) êÄåç, åÓÒÍ‚‡
‡Ë·ÓΠÔÓÔÛÎflÌÓÈ ÚÂÓËÂÈ Ô‡ÚÓ„ÂÌÂÁ‡ Ò‡ı‡ÌÓ„Ó ‰Ë‡·ÂÚ‡ (ëÑ) 1 ÚËÔ‡ ‚ Ú˜ÂÌË ÔÓÒΉÌËı 20 ÎÂÚ fl‚Îfl·Ҹ ÚÂÓËfl, 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 ̇˜‡Î‡ ‡ÛÚÓËÏÏÛÌÌ˚ı ÔÓˆÂÒÒÓ‚ fl‚Îfl˛ÚÒfl Ù‡ÍÚÓ˚ ‚̯ÌÂÈ
Ò‰˚. 燘‡Î¸Ì‡fl ÒÚ‡‰Ëfl ëÑ 1 ÚËÔ‡ – „Ë·Âθ ÓÒÚÓ‚ÍÓ‚˚ı ÍÎÂÚÓÍ – ÔÓÚÂ͇ÂÚ ·ÂÒÒËÏÔÚÓÏÌÓ, ÌÓ ÏÓÊÂÚ
·˚Ú¸ ‚˚fl‚ÎÂ̇ Ò ÔÓÏÓ˘¸˛ ÓÔ‰ÂÎÂÌËfl ‡ÛÚÓ‡ÌÚËÚÂÎ.
íÓθÍÓ Ì‡ ÔÓÒΉÌËı ÒÚ‡‰Ëflı ÔÓˆÂÒÒ‡, ÍÓ„‰‡ ÔÓ‰‡‚Îfl˛˘Â ·Óθ¯ËÌÒÚ‚Ó β-ÍÎÂÚÓÍ ÔÓ„Ë·‡ÂÚ Ë ‚ÓÁÌË͇ÂÚ
‡·ÒÓβÚ̇fl ̉ÓÒÚ‡ÚÓ˜ÌÓÒÚ¸ ËÌÒÛÎË̇, ÔÓfl‚Îfl˛ÚÒfl
ÍÎËÌ˘ÂÒÍË ÔËÁ̇ÍË ‰Ë‡·ÂÚ‡ (ËÒ. 1).
Ç Ì‡˜‡Î 1970-ı „Ó‰Ó‚ ËÒÒΉӂ‡ÌËfl, Ôӂ‰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 ÔÓÒÚÓÈ: ÔË Ì‡Î˘ËË ÓÔ‰ÂÎÂÌÌ˚ı ‡ÎÎÂÎÂÈ „ÂÌÓ‚ ÒËÒÚÂÏ˚ HLA ‰ÓÏËÌËÓ‚‡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‡ ÔÓÚflÊÂÌËË ÔÓÒΉÌËı ‰ÂÒflÚËÎÂÚËÈ ·˚ÎÓ ËÒÒΉӂ‡ÌÓ ÏÌÓÊÂÒÚ‚Ó Ù‡ÍÚÓÓ‚ ÓÍÛʇ˛˘ÂÈ Ò‰˚
Ò ˆÂθ˛ ‚˚fl‚ÎÂÌËfl ‰ÓÒÚÓ‚ÂÌÓ„Ó Í‡Ì‰Ë‰‡Ú‡, ‚ÎËfl˛˘Â„Ó Ì‡ Á‡·Ó΂‡ÌË ëÑ 1 ÚËÔ‡ [2]. ç‡ ÔÂ‚˚ı ÔÓ‡ı Ú‡ÍËÏË Í‡Ì‰Ë‰‡Ú‡ÏË Ò˜ËÚ‡ÎËÒ¸ ‚ËÛÒ˚ [23]. Ç
̇˜‡ÎÂ Ë ÒÂ‰ËÌ 80-ı „Ó‰Ó‚ ÔÓ¯ÎÓ„Ó ÒÚÓÎÂÚËfl
Û͇Á˚‚‡ÎÓÒ¸ ̇ Á̇˜ÂÌË ÔÓ‰ÓÎÊËÚÂθÌÓÒÚË „Û‰ÌÓ„Ó ‚Ò͇ÏÎË‚‡ÌËfl [11]. Ç Í‡˜ÂÒÚ‚Â Ô˘ËÌ˚ Á‡·Ó΂‡ÌËfl ̇Á˚‚‡ÎÓÒ¸ ÛÔÓÚ·ÎÂÌË ÍÓÓ‚¸Â„Ó ÏÓÎÓ͇
ËÎË ËÒÍÛÒÒÚ‚ÂÌÌÓ ‚Ò͇ÏÎË‚‡ÌË [14,30]. é‰Ì‡ÍÓ
ËÒÒΉӂ‡ÌËÂ, Ôӂ‰ÂÌÌÓ ‚ 2003 „. å.Ä. Atkinson
[6], Ì ÔÓ‰Ú‚Â‰ËÎÓ ÚÓÚ Ù‡ÍÚ, ˜ÚÓ 100% ÒÛ·˙ÂÍÚÓ‚,
ÒÚ‡‰‡˛˘Ëı ëÑ 1 ÚËÔ‡, ËÏÂ˛Ú ‡ÌÚËÚ· ÔÓÚË‚ ÏÓÎÂÍÛÎ˚ BSA (bovine serum albumin) [25].
èÓ ÔÓÒΉÌËÏ ‰‡ÌÌ˚Ï, ‡Á‚ËÚË ‡ÌÚË-β-ÍÎÂÚÓ˜ÌÓ„Ó ‡ÛÚÓËÏÏÛÌËÚÂÚ‡ Ò‚flÁ‡ÌÓ Ò ‚˚·ÓÓÏ ‚ÂÏÂÌË
‚Íβ˜ÂÌËfl ‚ ‡ˆËÓÌ ÔËÚ‡ÌËfl Ï·‰Â̈‚ ÁÂÌÓ‚˚ı
[8,34,42], ÛÔÓÚ·ÎÂÌË Á‡ÏÂÌËÚÂÎÂÈ Ò‡ı‡‡, ÍÓÙÂË̇ Ë ‰‡Ê ÍÓÔ˜ÂÌÓÈ ˚·˚ [4]. LJÊ̇fl Óθ ÓÚ‚Ó‰ËÚÒfl ÔËÓ‰ÌÓÏÛ ÍÓÏÔÓÌÂÌÚÛ; ÏÂÊ‰Û ‡Á΢Ì˚ÏË „ËÓ̇ÏË ÏË‡ ̇·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 ÓÒÚÓ‚ÍÓ‚˚Ï ÍÎÂÚÍ‡Ï (ICA)
[12]. àÏÂÌÌÓ ˝Ú‡ ‰‡Ú‡ ÔËÁ̇ÂÚÒfl ÏÌÓ„ËÏË Í‡Í ‰‡Ú‡
ÛÒÚ‡ÌÓ‚ÎÂÌËfl ‡ÛÚÓËÏÏÛÌÌÓ„Ó ı‡‡ÍÚÂ‡ 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 ÔË ËÁÛ˜ÂÌËË ëÑ 1
ÚËÔ‡. чÌÌ˚È ÏÂÚÓ‰ Ó͇Á‡ÎÒfl ̇˷ÓΠۉ‡˜Ì˚Ï Í‡Í
‚ ‰Ë‡„ÌÓÒÚËÍ Á‡·Ó΂‡ÌËfl, Ú‡Í Ë ÔË ‚˚fl‚ÎÂÌËË Îˈ
Ò ÔÓ‚˚¯ÂÌÌ˚Ï ËÒÍÓÏ ‡Á‚ËÚËfl ‰Ë‡·ÂÚ‡. àÒÒΉӂ‡ÌËfl, ÔÓÒ‚fl˘ÂÌÌ˚ ÔÓÙË·ÍÚËÍ Á‡·Ó΂‡ÌËfl, ·˚ÎË
·˚ Ì‚ÓÁÏÓÊÌ˚ ·ÂÁ ÓÔ‰ÂÎÂÌËfl ICA. é‰Ì‡ÍÓ ‚ ̇ÒÚÓfl˘Â ‚ÂÏfl Ò˜ËÚ‡ÂÚÒfl, ˜ÚÓ ÔÂ‚˘Ì˚Ï „ÛÏÓ‡Î¸Ì˚Ï Ï‡ÍÂÓÏ fl‚Îfl˛ÚÒfl ‡ÛÚÓ‡ÌÚËÚ· Í ÏÓÎÂÍÛΠËÌÒÛÎË̇, ‡ Ì ICA [3,17]. ÄÛÚÓ‡ÌÚËÚ· Í ËÌÒÛÎËÌÛ
(IAA) ı‡‡ÍÚÂËÁÛ˛ÚÒfl ‚˚ÒÓÍÓÈ ˜Û‚ÒÚ‚ËÚÂθÌÓÒÚ¸˛,
‡ÌÌËÏ ÔÓfl‚ÎÂÌËÂÏ Ë ·˚ÒÚ˚Ï ËÒ˜ÂÁÌÓ‚ÂÌËÂÏ. àı
Í‡ÚÍÓ‚ÂÏÂÌÌÓ ÔÓfl‚ÎÂÌË ÏÓÊÂÚ ·˚Ú¸ χÍÂÓÏ
ӷ̇ÛÊÂÌËfl ‰Û„Ëı ‡ÌÚËÚÂÎ ‚ ·ÓΠÔÓÁ‰ÌË ÒÓÍË.
Ç ˆÂÎflı ÔÓ‚˚¯ÂÌËfl ‰ÓÒÚÓ‚ÂÌÓÒÚË ÂÁÛθڇÚÓ‚ ÌÂÓ·ıÓ‰ËÏÓ ËÒÔÓθÁÓ‚‡ÌË ‡Á΢Ì˚ı „ÛÔÔ ‡ÌÚËÚÂÎ.
ëÙÓÏËÓ‚‡ÎÓÒ¸ ÏÌÂÌËÂ, ˜ÚÓ ÒËÏÔÚÓÏ˚ ëÑ 1 ÚËÔ‡
Ó·˚˜ÌÓ ÔÓfl‚Îfl˛ÚÒfl, ÍÓ„‰‡ 90–95% β-ÍÎÂÚÓÍ ÔÓ„Ë·ÎË
[15]. àÒÒΉӂ‡ÌËfl ‰ÓÍÚÓ‡ W. Gepts, Ôӂ‰ÂÌÌ˚ ̇
Ô‡ÚÓÎӄӇ̇ڇÏ˘ÂÒÍÓÏ Ï‡ÚÂˇÎÂ, ˜‡ÒÚ˘ÌÓ ÔÓ‰Ú‚Âʉ‡˛Ú ˝ÚÓÚ Ù‡ÍÚ [18]. íÂÏ Ì ÏÂÌÂÂ, Í‡Í ÔÓ͇Á‡ÎË
ÔÓÒΉÌË ËÒÒΉӂ‡ÌËfl, ÒÂÍˆËfl ËÌÒÛÎË̇ ‚ ıÓ‰Â
ÚÂÒÚÓ‚ ÒÓ Òϯ‡ÌÌ˚Ï ÔËÚ‡ÌËÂÏ Û ·ÓθÌ˚ı Ò ‚ÔÂ‚˚Â
‚˚fl‚ÎÂÌÌ˚Ï ëÑ ÒÓÒÚ‡‚ÎflÂÚ ÔÓÎÓ‚ËÌÛ ÔÓ Ò‡‚ÌÂÌ˲ Ò
ÍÓÌÚÓθÌÓÈ „ÛÔÔÓÈ Á‰ÓÓ‚˚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
ÔË ÓʉÂÌËË ËÏÂÂÚ 100% ËÎË ÔÓ˜ÚË 100% «ÌÓχθÌ˚» Ò‚ÓËı β-ÍÎÂÚÓÍ. ÑÓ Ì‡ÒÚÓfl˘Â„Ó ‚ÂÏÂÌË ‚ ÒËÎÛ
Ô‡ÍÚ˘ÂÒÍËı ÚÛ‰ÌÓÒÚÂÈ ‚Ò ¢ Ì‚ÓÁÏÓÊÌÓ ÚÓ˜ÌÓ
ÓÔ‰ÂÎËÚ¸ Û ˜ÂÎÓ‚Â͇ ÓÒÚÓ‚ÍÓ‚Û˛ ÍÎÂÚÓ˜ÌÛ˛ χÒÒÛ
in vivo ËÎË ex vivo, ‚ ÓÔÛ·ÎËÍÓ‚‡ÌÌÓÈ ÔÓ ‰‡ÌÌÓÏÛ ‚ÓÔÓÒÛ ÎËÚÂ‡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 ÔÂËÓ‰˚ ÒÚÛÔÂ̘‡ÚÓÈ ÂÏËÒÒËË, ÏÓÊÂÚ ÎË ÔÓËÒıÓ‰ËÚ¸ ÔÓˆÂÒÒ „ÂÌÂ‡ˆËË β-ÍÎÂÚÓÍ
[19,21]; ͇ÍÓ‚Ó ‚ÎËflÌË هÍÚÓÓ‚ ‚ÓÁ‡ÒÚ‡, ÔÓ· Ë „ÂÌÂÚËÍË Ì‡ ˝ÚÓÚ „‡‰ËÂÌÚ, Ë ÍÓ„‰‡ ‰‡ÌÌ˚È ÔÓˆÂÒÒ Ì‡˜Ë̇ÂÚÒfl. ç‡ÍÓ̈, Íβ˜Â‚ÓÈ ÔÓ·ÎÂÏÓÈ, ÓÒÓ·ÂÌÌÓ
‰Îfl ËÏÏÛÌÓÎÓ„Ó‚, ÓÒÚ‡ÂÚÒfl ÌÂÓ·ıÓ‰ËÏÓÒÚ¸ ‚˚flÒÌÂÌËfl
‚ÓÔÓÒ‡, ÔÓ˜ÂÏÛ ‡ÁÛ¯ÂÌË β-ÍÎÂÚÓÍ Ó·˚˜ÌÓ ÔÓËÒ-
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 ÔÂËÓ‰ ÓÚ ÌÂÒÍÓθÍËı ÏÂÒflˆÂ‚ ‰Ó ÌÂÒÍÓθÍËı ÎÂÚ, ‡ ÚÓ Ë ‰ÂÒflÚËÎÂÚËÈ, ‚ ÓÚ΢ˠÓÚ ‡͈ËË ÓÚÚÓÊÂÌËfl Ú‡ÌÒÔ·ÌÚ‡ÌÚ‡ ËÎË ÏÌÓ„Ëı ‰Û„Ëı ËÏÏÛÌÌ˚ı ‡͈ËÈ, ÍÓÚÓ˚ ÔÓÚÂ͇˛Ú ‚
Ú˜ÂÌË ÌÂÒÍÓθÍËı ˜‡ÒÓ‚ ËÎË ÌÂÒÍÓθÍËı ‰ÌÂÈ [35].
ä‡ÈÌ ‚‡ÊÌÓÈ fl‚ÎflÂÚÒfl ÔÓ·ÎÂχ ̇Û¯ÂÌËfl
„ÛÎflˆËË ËÏÏÛÌÌÓ„Ó ÓÚ‚ÂÚ‡ ‚ ÓÚÌÓ¯ÂÌËË ÒÓ·ÒÚ‚ÂÌÌ˚ı ÍÎÂÚÓÍ (β-ÍÎÂÚÓÍ), Ú. Í. ËÏÏÛÌ̇fl ÒËÒÚÂχ Ó͇Á˚‚‡ÂÚ ‚ÎËflÌË ̇ ÔÓˆÂÒÒ Á‡·Ó΂‡ÌËfl Á‡‰ÓÎ„Ó ‰Ó
ÔÓfl‚ÎÂÌËfl ÍÎËÌ˘ÂÒÍËı ÒËÏÔÚÓÏÓ‚ Ò‡ı‡ÌÓ„Ó ‰Ë‡·ÂÚ‡. èÓÒΉÌË ËÒÒΉӂ‡ÌËfl „Ó‚ÓflÚ Ó ÚÓÏ, ˜ÚÓ
̇Û¯ÂÌËfl ÌÓχθÌÓÈ „ÛÎflˆËË ‡ÛÚÓ‡ÍÚË‚ÌÓ„Ó
Ë ‡ÛÚÓÔÓÚÂÍÚË‚ÌÓ„Ó ËÏÏÛÌÌÓ„Ó ÓÚ‚ÂÚ‡ ÏÓ„ÛÚ fl‚ÎflÚ¸Òfl ÂÁÛθڇÚÓÏ ÌÂÔ‡‚ËθÌÓ„Ó ÙÛÌ͈ËÓÌËÓ‚‡ÌËfl ÔÓÔÛÎflˆËË í-ÍÎÂÚÓÍ, ÍÓÚÓ˚ ‡ÒÔÓÁ̇˛ÚÒfl ÔÓ
˝ÍÒÔÂÒÒËË 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 ÔÂÔflÚÒÚ‚Û˛˘ËÏË ‡Á‚ËÚ˲ ëÑ 1 ÚËÔ‡. äÓÏ ÚÓ„Ó, ‡ÒÒχÚË‚‡ÂÚÒfl Ù‡ÍÚ, ˜ÚÓ
˝ÚË „ÂÌ˚ Ù‡ÍÚ˘ÂÒÍË ‚ÎËfl˛Ú ̇ ‚ÓÒÔËËϘ˂ÓÒÚ¸ Ë
ÒÓÔÓÚË‚ÎflÂÏÓÒÚ¸ Í CÑ 1 ÚËÔ‡ ‚ ıӉ ‚ÒÂ„Ó ÔÂËÓ‰‡,
Ô‰¯ÂÒÚ‚Û˛˘Â„Ó Á‡·Ó΂‡Ì˲ ‰Ë‡·ÂÚÓÏ, ‡ Ì ÚÓθÍÓ
‚ ÔÂËÓ‰, Ô‰¯ÂÒÚ‚Û˛˘ËÈ ‡ÛÚÓËÏÏÛÌÌÓÈ Ë̉Û͈ËË.
èË ÓˆÂÌÍ ‚ÎËflÌËfl Ù‡ÍÚÓÓ‚ ÓÍÛʇ˛˘ÂÈ Ò‰˚ ̇
‡Á‚ËÚË ҇ı‡ÌÓ„Ó ‰Ë‡·ÂÚ‡ 1 ÚËÔ‡ ‡ÒÒχÚË‚‡˛ÚÒfl
‡Á΢Ì˚ ÔËÓ‰Ì˚ ÔÓˆÂÒÒ˚, Ó͇Á˚‚‡˛˘Ë ‚ÓÁ‰ÂÈÒÚ‚Ë ̇ Ú˜ÂÌË ‰Ë‡·ÂÚ‡ Á‡ ‚ÂÒ¸ ÔÂËÓ‰ Á‡·Ó΂‡ÌËfl, ‚Íβ˜‡fl Ë Â„Ó ‰ÓÍÎËÌ˘ÂÒÍÛ˛ ÒÚ‡‰Ë˛, ‡ Ì ÚÓθ-
ÍÓ Ù‡ÍÚÓ, ÔÓ‚ÓˆËÛ˛˘ËÈ ÍÎËÌ˘ÂÒÍËÈ ‰Â·˛Ú Á‡·Ó΂‡ÌËfl, ̇ÔËÏÂ ‚ËÛÒ̇fl ËÌÙÂ͈Ëfl.
ÑÛ„ËÏ ‡ÒÔÂÍÚÓÏ, ÍÓÚÓ˚È ÌÂÓ·ıÓ‰ËÏÓ ÔÂÂÒÏÓÚÂÚ¸, fl‚ÎflÂÚÒfl ÙÂÌÓÏÂÌ ÔÓÚÂË β-ÍÎÂÚÓÍ; ÂÒÚ¸ ‚ÂÓflÚÌÓÒÚ¸ 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
„ÂÌÂ‡ˆËË [22]. Ç Ì‡ÒÚÓfl˘Â ‚ÂÏfl ‰Ó ÍÓ̈‡ ÌÂflÒÌ˚Ï ÓÒÚ‡ÂÚÒfl ÏÂı‡ÌËÁÏ ‡ÛÚÓËÏÏÛÌÌÓÈ ‡͈ËË,
Ô‰‚‡fl˛˘ÂÈ ‡ÒÔ‡‰ β-ÍÎÂÚÓÍ, ‚ ÓÒÓ·ÂÌÌÓÒÚË ‡͈Ëfl 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 ÔÓËÒıÓ‰ËÚ¸
‚ ÂÁÛθڇÚ ‡ÁÌ˚ı Ô‡ÚÓÎӄ˘ÂÒÍËı ÔÓˆÂÒÒÓ‚.
é‰ËÌ ËÁ ÌËı – ‰ÂÒÚÛ͈Ëfl ËÎË ÌÂÍÓÁ β-ÍÎÂÚÓÍ,
‰Û„ÓÈ – ‡ÔÓÔÚÓÁ ËÎË „ÂÌÂÚ˘ÂÒÍË Á‡ÔÓ„‡ÏÏËÓ‚‡ÌÌ˚È ÔÓˆÂÒÒ „Ë·ÂÎË ÍÎÂÚÓÍ.
çÂÍÓÁ – ˝ÚÓ Ô‡ÚÓÎӄ˘ÂÒÍËÈ ÔÓˆÂÒÒ, ‡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 ‚ËÛÒ‡. çÂÍÓÁ ÒÓÔÓ‚Óʉ‡ÂÚÒfl ÓÚÂÍÓÏ ÍÎÂÚÍË, ‡ÌÌÂÈ
ÔÓÚÂÂÈ ˆÂÎÓÒÚÌÓÒÚË Â ÏÂÏ·‡Ì˚, ÔÓ‚ÂʉÂÌËÂÏ
ÏËÚÓıÓ̉ËÈ Ë ‰Û„Ëı Ó„‡ÌÂÎÎ, ˜ÚÓ ‚ ÍÓ̘ÌÓÏ
Ò˜ÂÚ Á‡Í‡Ì˜Ë‚‡ÂÚÒfl ÎËÁËÒÓÏ ÓÒÚ‡ÚÍÓ‚ ÍÎÂÚÍË [1].
çÂÍÓÁ ÍÎÂÚÍË ÒÚ‡ÌÓ‚ËÚÒfl Ô˘ËÌÓÈ ÔÓ‚ÂʉÂÌËfl Ë ‚ÓÒÔ‡ÎÂÌËfl ÓÍÛʇ˛˘Ëı ÍÎÂÚÓÍ Ë ‚ˉÂÌ Ì‡
ÒÂÁ Ú͇ÌÂÈ.
β-äÎÂÚÍË ÔÓ‰‚Â„‡˛ÚÒfl ÌÂÍÓÁÛ ‚ ÔËÒÛÚÒÚ‚ËË
ËÁ·˚ÚÓ˜ÌÓ„Ó ÍÓ΢ÂÒÚ‚‡ Ò‚Ó·Ó‰Ì˚ı ‡‰Ë͇ÎÓ‚ –
ÍËÒÎÓÓ‰Ì˚ı ‡‰Ë͇ÎÓ‚ ËÎË ÓÍÒˉ‡ ‡ÁÓÚ‡ ËÎË ÔÓ‰
3/2006
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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 ÔÓ‚ÓÒÔ‡ÎËÚÂθÌ˚ı ˆËÚÓÍËÌÓ‚. çÂÍÓÁ
Ì ҂flÁ‡Ì Ò ÔÓÚ·ÎÂÌËÂÏ ˝ÌÂ„ËË Ë ÒËÌÚÂÁÓÏ ·ÂÎ͇,
ÚÓ„‰‡ Í‡Í ‡ÔÓÔÚÓÁ – ˝ÚÓ ˝ÌÂ„ÓÁ‡‚ËÒËÏ˚È ÔÓˆÂÒÒ.
íÂÏËÌ «‡ÔÓÔÚÓÁ» ÒÓÓÚ‚ÂÚÒÚ‚ÛÂÚ ÛÒÒÍÓÏÛ «ÎËÒÚÓÔ‡‰», ‚ ÔÓˆÂÒÒ ‡ÔÓÔÚÓÁ‡ ÍÎÂÚ͇ ËÒ˜ÂÁ‡ÂÚ ‚ Ú˜ÂÌËÂ
15–120 ÏËÌ. Ç ·Óθ¯ËÌÒÚ‚Â ÒÎÛ˜‡Â‚ ‡ÔÓÔÚÓÁ Ò‚flÁ‡Ì Ò ‡ÍÚË‚‡ˆËÂÈ ÒÔˆËÙ˘ÂÒÍËı ˆËÒÚÂËÌÓ‚˚ı ÔÓÚ‡Á – ͇ÒÔ‡Á,
ÒÛ˘ÂÒÚ‚Û˛˘Ëı ‚ ÍÎÂÚÍ ‚ ‚ˉ Ì‡ÍÚË‚Ì˚ı ÙÓÏ – ÔÓ͇ÒÔ‡Á. Ç Ì‡Á‚‡ÌËË «Caspase» ÓÚ‡ÊÂÌ ÏÂı‡ÌËÁÏ ÔÓÚÂÓÎËÁ‡: ‚ ‡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 ÔÓËÒıÓ‰ËÚ ‡ÁÛ¯ÂÌË ·ÂÎÍÓ‚, Û˜‡ÒÚ‚Û˛˘Ëı ‚ ÙÓÏËÓ‚‡ÌËË ˆËÚÓÒÍÂÎÂÚ‡; „ˉÓÎËÁ ·ÂÎÍÓ‚ fl‰ÂÌÓÈ ÏÂÏ·‡Ì˚, ÍÓ̉ÂÌÒ‡ˆËfl ıÓχÚË̇;
‡Ò˘ÂÔÎÂÌË ‡ÌÚˇÔÓÔÚÓÁÌ˚ı ·ÂÎÍÓ‚ ÒÂÏÂÈÒÚ‚‡ ÇÒl-2;
ÔÓÚÂÓÎËÁ 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·ÓÔÓÎËÏÂ‡Á‡).
ëÛ˘ÂÒÚ‚ÛÂÚ ÌÂÒÍÓθÍÓ ÔÛÚÂÈ ‡ÎËÁ‡ˆËË ÔÓ„‡ÏÏ˚ ÍÎÂÚÓ˜ÌÓÈ ÒÏÂÚË: Ò Û˜‡ÒÚËÂÏ ˆÂÔÚÓÓ‚
Ô·ÁχÚ˘ÂÒÍÓÈ ÏÂÏ·‡Ì˚; Ò Û˜‡ÒÚËÂÏ ÏËÚÓıÓ̉ˇθÌÓ„Ó ˆËÚÓıÓχ 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-ÍËÎÎÂ‡, ‡ÍÚË‚ËÛÂÚÒfl
Ë Á‡ÔÛÒ͇ÂÚ ÔÓ„‡ÏÏÛ „Ë·ÂÎË ÍÎÂÚÍË [16].
èË ‡ÍÚË‚‡ˆËË Í‡ÒÔ‡Á˚ ÔÂ‚Ó„Ó ˝¯ÂÎÓ̇ ÊËÁ̸
ÍÎÂÚÍË Â˘Â ÏÓÊÌÓ ÒÓı‡ÌËÚ¸. ëÛ˘ÂÒÚ‚Û˛Ú „ÛÎflÚÓ-
62
3/2006
˚, ÍÓÚÓ˚ ·ÎÓÍËÛ˛Ú ËÎË Ì‡Ó·ÓÓÚ ÛÒËÎË‚‡˛Ú ‡ÁÛ¯ËÚÂθÌÓ ‰ÂÈÒÚ‚Ë ͇ÒÔ‡Á ÔÂ‚Ó„Ó ˝¯ÂÎÓ̇. èË
‡ÍÚË‚‡ˆËË Í‡ÒÔ‡Á ‚ÚÓÓ„Ó ˝¯ÂÎÓ̇ (˝ÙÙÂÍÚÓÌ˚ı ͇ÒÔ‡Á) ÔÓˆÂÒÒ, Á‡ÔÛ˘ÂÌÌ˚È ÔÓ„‡ÏÏÓÈ ÒÏÂÚË, Ó͇Á˚‚‡ÂÚÒfl ÌÂÓ·‡ÚËÏ˚Ï. ÑÛ„ÓÈ ÔÛÚ¸ ‡ÎËÁ‡ˆËË ÔÓ„‡ÏÏ˚ ‡ÔÓÔÚÓÁ‡ Á‡‚ËÒËÚ ÓÚ ÏËÚÓıÓ̉ˇθÌÓ„Ó ˆËÚÓıÓχ ë. èË ÔÓ‚ÂʉÂÌËË ÏËÚÓıÓ̉ËÈ, ̇ÔËÏÂ
ÔË ËÒÚÓ˘ÂÌËË ÍÎÂÚÓÍ, ‚ÓÒÒÚ‡ÌÓ‚ÎÂÌÌ˚Ï „βڇÚËÓÌÓÏ ËÎË çÄÑîç, ÔÓËÒıÓ‰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‚ÓËÏ˚ı ·ÂÎÍÓ‚ ÏÂÊÏÂÏ·‡ÌÌÓ„Ó ÔÓÒÚ‡ÌÒÚ‚‡, ÒÂ‰Ë ÌËı – ‡ÔÓÔÚÓ„ÂÌÌ˚ هÍÚÓ˚, ˆËÚÓıÓÏ ë Ë ÔÓ͇ÒÔ‡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. èÓ„‡ÏÏËÛÂχfl ÍÎÂÚӘ̇fl ÒÏÂÚ¸ ÏÓÊÂÚ ·˚Ú¸ ‡ÎËÁÓ‚‡Ì‡ ‚ ÂÁÛθڇÚ ÍÓÏ·ËÌËÓ‚‡ÌÌÓ„Ó
‰ÂÈÒÚ‚Ëfl ‰‚Ûı ÔÛÚÂÈ – Ò Û˜‡ÒÚËÂÏ Ë ˆÂÔÚÓÓ‚ Ô·ÁχÚ˘ÂÒÍÓÈ ÏÂÏ·‡Ì˚ Ë ÏËÚÓıÓ̉ˇθÌÓ„Ó ˆËÚÓıÓχ ë.
Ç ÔÓÒΉÌË „Ó‰˚ ·˚ÎÓ ÔÓ͇Á‡ÌÓ, ˜ÚÓ ÔÓˆÂÒÒ˚
ÌÂÍÓÁ‡ Ë ‡ÔÓÔÚÓÁ‡ Ì ÔÓÚË‚ÓÒÚÓflÚ ‰Û„ ‰Û„Û.
LJÊÌÛ˛ Óθ ‚ ÔÓˆÂÒÒ ÍÎÂÚÓ˜ÌÓÈ „Ë·ÂÎË Ë„‡˛Ú
ˆËÚÓÍËÌ˚ – ÒÂÍÂÚÓÌ˚ ·ÂÎÍË, ‚˚ÔÓÎÌfl˛˘ËÂ
ÙÛÌÍˆË˛ ωˇÚÓÓ‚ ÏÂÊÍÎÂÚÓ˜Ì˚ı Ò˄̇ÎÓ‚ Ë ÓÒÌÓ‚Ì˚ı „ÛÎflÚÓÓ‚ ‡ÍÚË‚ÌÓÒÚË ËÏÏÛÌÌÓÈ ÒËÒÚÂÏ˚.
ñËÚÓÍËÌ˚ ̇Á˚‚‡˛Ú «·ÂÎ͇ÏË Ò‚flÁË». Ç Á‡‚ËÒËÏÓÒÚË ÓÚ Ó·ÂÒÔ˜ÂÌËfl ÍÎÂÚÓ˜Ì˚ı ËÎË „ÛÏÓ‡Î¸Ì˚ı
ÙÓÏ ËÏÏÛÌÌÓ„Ó ÓÚ‚ÂÚ‡ ˆËÚÓÍËÌ˚ ÏÓ„ÛÚ ·˚Ú¸ ÓÚÌÂÒÂÌ˚ Í Th1 ËÎË Í Th2 ıÂÎÔÂÌ˚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‚ËÓ‚‡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‡, ̇Ô‡‚ÎÂÌÌ˚ı ̇ ËÁÛ˜ÂÌË ̇Û¯ÂÌËÈ ÙÛÌ͈ËÈ ËÏÏÛÌÌÓÈ ÒËÒÚÂÏ˚, ËÒÔÓθÁÓ‚‡Î‡Ò¸ ‚ ͇˜ÂÒÚ‚Â
χÚÂˇ· ÍÓ‚¸ ËÁ ÔÂËÙÂ˘ÂÒÍËı ‚ÂÌ, ‚ ÚÓ ‚ÂÏfl
Í‡Í Ó˜‡„ÓÏ ıÓÌ˘ÂÒÍÓ„Ó ‚ÓÒÔ‡ÎÂÌËfl ÔË ‰Ë‡·ÂÚ fl‚ÎflÂÚÒfl ÔÓ‰ÊÂÎۉӘ̇fl ÊÂÎÂÁ‡. é˜Â‚ˉÌÓ, ˜ÚÓ ÔӉӷ̇fl ‡ÁÌˈ‡ ÔË ËÒÒΉӂ‡ÌËË Ï‡ÚÂˇ· ‚˚Á˚‚‡ÂÚ
ÌÂχÎÓ ÍÓ΢ÂÒÚ‚Ó Ó¯Ë·ÓÍ Ë ‡ÚÂÙ‡ÍÚÓ‚ [10,6].
Ç ıӉ Ô‡ÍÚ˘ÂÒÍËı ËÒÒΉӂ‡ÌËÈ, ÔÓÒ‚fl˘ÂÌÌ˚ı
ÔÓÙË·ÍÚËÍ Á‡·Ó΂‡ÂÏÓÒÚË, ÒÛ˘ÂÒÚ‚ÛÂÚ ÏÌÓ„Ó ÔÂÔflÚÒÚ‚ËÈ. ëÂ‰Ë ÌËı ˝Ú˘ÂÒÍË ‡ÒÔÂÍÚ˚, ‚Íβ˜‡˛˘ËÂ
Ê·ÌË ԇˆËÂÌÚÓ‚ Á̇ڸ Ó ‡Á‚ËÚËË Á‡·Ó΂‡ÌËfl ‚ ·Û‰Û˘ÂÏ, ‚ÓÁÏÓÊÌÓÒÚ¸ Ôӂ‰ÂÌËfl Ú‡ÍÓ„Ó Ó‰‡ ÒÍËÌËÌ„‡ ÔË ÓÚÒÛÚÒÚ‚ËË ÏÂÚÓ‰Ó‚ Ô‰ÛÔÂʉÂÌËfl Á‡·Ó΂‡ÂÏÓÒÚË ëÑ 1 ÚËÔ‡, ̇Û¯ÂÌË ÍÓÌÙˉÂ̈ˇθÌÓÒÚË, ‚ÓÔÓÒ˚ Ó„‡ÌËÁ‡ˆËË Ô‡ÍÚ˘ÂÒÍÓ„Ó ÓÒÛ˘ÂÒÚ‚ÎÂÌËfl
ÒÍËÌËÌ„‡ Ë, ÍÓ̘ÌÓ, ÙË̇ÌÒÓ‚˚ ·‡¸Â˚ [20]. èÂ‚Ó̇˜‡Î¸Ì˚È ÓÔÚËÏËÁÏ ËÒÒΉӂ‡ÚÂÎÂÈ, ͇҇˛˘ËÈÒfl
ˉÂÌÚËÙË͇ˆËË ÏÂÚÓ‰‡ Ô‰ÛÔÂʉÂÌËfl Á‡·Ó΂‡ÂÏÓÒÚË ëÑ 1 ÚËÔ‡ ÔË ËÒÔÓθÁÓ‚‡ÌËË ÊË‚ÓÚÌ˚ı ÏÓ‰ÂÎÂÈ,
ÔË‚ÂÎ Í‡Í Í ÓÚÍ˚ÚËflÏ, Ú‡Í Ë Í ‡ÁÓ˜‡Ó‚‡ÌËflÏ ‚ ÓÚÌÓ¯ÂÌËË ÔËÏÂÌÂÌËfl ‡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‰ÛÔÂʉÂÌËfl 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 ÔÓˆÂÒÒ Ô‰ÛÔÂʉÂÌËfl
Способность
предотвратить CД1 типа
Начало клинически
явного СД 1 типа
Á‡·Ó΂‡ÂÏÓÒÚË ‰Ë‡·ÂÚÓÏ Û Ï˚¯ÂÈ Ó͇Á˚‚‡ÂÚÒfl ÓÚÌÓÒËÚÂθÌÓ ÔÓÒÚ˚Ï, ‡ Û Î˛‰ÂÈ ˜ÂÁ‚˚˜‡ÈÌÓ ÒÎÓÊÌ˚Ï?
é‰ÌÓÈ ËÁ Ô˘ËÌ ÏÓÊÂÚ fl‚ÎflÚ¸Òfl ÚÓ, ˜ÚÓ ·Óθ¯ÂÂ
Á̇˜ÂÌË Ôˉ‡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‡‡ÍÚÂËÁÛ˛ÚÒfl ̇Û¯ÂÌËflÏË ‚ „ÛÎflˆËË ËÏÏÛÌÌÓ„Ó ÓÚ‚ÂÚ‡ Ë
ÒÔÓÒÓ·ÌÓÒÚ¸˛ Í ÂÏËÒÒËË Á‡·Ó΂‡ÌËfl ÔÓÒΠÚ‡ÌÒÔ·ÌÚ‡ˆËË ÍÓÒÚÌÓ„Ó ÏÓÁ„‡. íÂÏ Ì ÏÂÌÂÂ, ËÏÂÂÚÒfl Ë
fl‰ ÒÛ˘ÂÒÚ‚ÂÌÌ˚ı ÓÚ΢ËÈ [28]: ÔÓ͇Á‡ÌÓ ‡Á΢ÌÓÂ
‰ÂÈÒÚ‚Ë χÚÂËÌÒÍËı ‡ÛÚÓ‡ÌÚËÚÂÎ Û Ï˚¯Ë Ë Û ˜ÂÎÓ‚Â͇; ‡Á΢Ëfl ̇·Î˛‰‡˛ÚÒfl Ë ‚ ˜‡ÒÚÓÚ Á‡·Ó΂‡ÂÏÓÒÚË Ë ÔÓÎÓ‚ÓÈ ÔË̇‰ÎÂÊÌÓÒÚË; ËÌÒÛÎËÚ Û NOD-Ï˚¯ÂÈ ÔÓÚÂ͇ÂÚ ‚ ΄ÍÓÈ ÙÓÏÂ, ‰Ó·Ó͇˜ÂÒÚ‚ÂÌÌÓ.
ç‡ÍÓ̈, ÙÛÌ͈ËÓÌËÓ‚‡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», ‚ ÍÓÚÓÓÈ ÒÔÓÒÓ·ÌÓÒÚ¸ Ô‰Ò͇Á˚‚‡Ú¸ ëÑ 1 ÚËÔ‡ Ë ÒÔÓÒÓ·ÌÓÒÚ¸ Ô‰ÓÚ‚‡˘‡Ú¸ ˝ÚÓ Á‡·Ó΂‡ÌË Ô‰ÒÚ‡‚ÎÂÌ˚
‰‚ÛÏfl ÎËÌËflÏË, ̇Ô‡‚ÎÂÌÌ˚ÏË ‚ ÔÓÚË‚ÓÔÓÎÓÊÌ˚ ÒÚÓÓÌ˚ [4] (ËÒ. 4).
ç‡ ‡ÌÌËı ÒÚ‡‰Ëflı ÔÓˆÂÒÒ‡ ÚÓ˜ÌÓÒÚ¸ Ô‰Ò͇Á‡ÌËfl
ÌËÊÂ, ˜ÂÏ ‚ ÔÂËÓ‰, ÍÓ„‰‡ ÔÓfl‚Îfl˛ÚÒfl ÔÂ‚˚ ÒËÏÔÚÓÏ˚ ‰Ë‡·ÂÚ‡, ÌÓ ˜ÂÏ ‡Ì¸¯Â ̇˜‡ÚÓ Î˜ÂÌË ÔÂÔ‡‡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
ÚÂ‡ÔËfl ÏÂÌ ˝ÙÙÂÍÚ˂̇. èË Ôӂ‰ÂÌËË ÚÂ‡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.
ëÓÓÍ ÎÂÚ Ì‡Á‡‰ ·˚ÎÓ ÓÚϘÂÌÓ, ˜ÚÓ ‚ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ ·ÓθÌ˚ı Ò Ì‰‡‚ÌÓ ‰Ë‡„ÌÓÒÚˆËÓ‚‡ÌÌ˚Ï ëÑ 1 ÚËÔ‡ ÓÒÚÓ‚ÍÓ‚˚ ÍÎÂÚÍË Ì‡˜Ë̇˛Ú
ÓÚÒÓ‰ËÌflÚ¸Òfl ÓÚ Ô‡ÌÍ‡Ú˘ÂÒÍËı ÔÓÚÓÍÓ‚. äÓÏÂ
ÚÓ„Ó, β-ÍÎÂÚÍË, ÒÔÓÒÓ·Ì˚ ÒÂÍÂÚËÓ‚‡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-„ÂÌÂ‡ÚË‚ÌÓÈ ÒÔÓÒÓ·ÌÓÒÚË β-ÍÎÂÚÓÍ. 燘‡ÎÓ
„ËÔÂ„ÎËÍÂÏËË ‰ÂÈÒÚ‚ËÚÂθÌÓ ÏÓÊÂÚ ‡ÒÒÓˆËËÓ‚‡Ú¸Òfl Ò ·Óθ¯ÂÈ ÓÒÚÓ‚ÍÓ‚ÓÈ ÍÎÂÚÓ˜ÌÓÈ Ï‡ÒÒÓÈ,
˜ÂÏ ÔÓ·„‡ÎË ‡ÌÂÂ.
èÂÒÔÂÍÚË‚Ì˚Ï Ô‰ÒÚ‡‚ÎflÂÚÒfl ËÁÛ˜ÂÌË ÒÔÓÒÓ·ÌÓÒÚË β-ÍÎÂÚÓÍ Í „ÂÌÂ‡ˆËË Ë ‡ÒÒÏÓÚÂÌËÂ
ÏÓ‰ÂÎË „ÂÌÂ‡ˆËË ÓÒÚÓ‚ÍÓ‚˚ı ÍÎÂÚÓÍ Û ·ÓθÌ˚ı
Ò ‚ÔÂ‚˚ ‚˚fl‚ÎÂÌÌ˚Ï ëÑ 1 ÚËÔ‡.
Литература
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