Влияние эстрогенов на обучение крыс с хроническим холинергическим дефицитом в мозге в водном тесте Морриса. Выделение компонента ''Пассивного плавания''

ÜìêçÄã ÇõëòÖâ çÖêÇçéâ ÑÖüíÖãúçéëíà, 2003, ÚÓÏ 53, ‹ 2, Ò. 208–214

˝ÍÒÔÂËÏÂÌڇθ̇fl Ô‡ÚÓÎÓ„Ëfl ‚˚Ò¯ÂÈ ÌÂ‚ÌÓÈ ‰ÂflÚÂθÌÓÒÚË ìÑä 591.513 + 612.8

ÇÎËflÌË ˝ÒÚÓ„ÂÌÓ‚ ̇ Ó·Û˜ÂÌË Í˚Ò Ò ıÓÌ˘ÂÒÍËÏ ıÓÎËÌÂ„˘ÂÒÍËÏ ‰ÂÙˈËÚÓÏ ‚ ÏÓÁ„ ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡. Ç˚‰ÂÎÂÌË ÍÓÏÔÓÌÂÌÚ‡ “Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl” © 2003 „. í. Ç. åÛıË̇, ç. ç. ãÂÏÓÌÚÓ‚‡, É. à. LJ̸ÍËÌ, å. éÂÚÚÂθ*, Ç. ä. è˙˜Â‚*, ë. é. Ň˜ÛËÌ ã‡·Ó‡ÚÓËfl ÌÂÈÓıËÏËË àÌÒÚËÚÛÚ‡ ÙËÁËÓÎӄ˘ÂÒÍË ‡ÍÚË‚Ì˚ı ‚¢ÂÒÚ‚ êÄç, óÂÌÓ„ÓÎӂ͇, e-mail [email protected], äÓÏÔ‡ÌËfl “âÂ̇هÏ”*, âÂ̇, ÉÂχÌËfl èÓÒÚÛÔË· ‚ ‰‡ÍˆË˛ 19.03.2002 „. èËÌflÚ‡ ‚ Ô˜‡Ú¸ 29.05.2002 „.

ïÓÌ˘ÂÒÍÓ ÒÌËÊÂÌË ıÓÎËÌÂ„˘ÂÒÍËı ÙÛÌ͈ËÈ ÏÓÁ„‡ ÔË ‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚ÓÏ ‚‚‰ÂÌËË ÌÂÈÓÚÓÍÒË̇ AF64A ÒÓÔÓ‚Óʉ‡ÂÚÒfl Û‚Â΢ÂÌËÂÏ Î‡ÚÂÌÚÌÓ„Ó ÔÂËÓ‰‡ ̇ıÓʉÂÌËfl Ì‚ˉËÏÓÈ Ô·ÚÙÓÏ˚ ÔË Ó·Û˜ÂÌËË Í˚Ò ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡ ÔÓ Ò‡‚ÌÂÌ˲ Ò ÍÓÌÚÓθÌ˚ÏË ÎÓÊÌÓÓÔÂËÓ‚‡ÌÌ˚ÏË ÊË‚ÓÚÌ˚ÏË. ê„ËÒÚ‡ˆËfl Ú‡ÂÍÚÓËÈ ‰‚ËÊÂÌËfl Í˚Ò Ò ÔÓÏÓ˘¸˛ ‚ˉÂÓ͇ÏÂ˚ Ë ÓË„Ë̇θÌÓÈ ÍÓÏÔ¸˛ÚÂÌÓÈ ÔÓ„‡ÏÏ˚ “Behavioral Vision” ÔÓ͇Á‡Î‡, ˜ÚÓ ‚‚‰ÂÌË 17β-˝ÒÚ‡‰ËÓ· Ë Â„Ó ÒËÌÚÂÚ˘ÂÒÍÓ„Ó ËÁÓÏÂ‡ J-861 (0.2 Ï„/Í„ per os Âʉ̂ÌÓ ‚ Ú˜ÂÌË 7 ‰ÌÂÈ ‰Ó Ë 10 ‰ÌÂÈ ÔÓÒΠӉÌÓÍ‡ÚÌÓ„Ó ‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚Ó„Ó ‚‚‰ÂÌËfl AF64A) ÛÎÛ˜¯‡ÂÚ Ó·Û˜ÂÌËÂ. ç‡Ô‡‚ÎÂÌÌÓÒÚ¸ Ú‡ÂÍÚÓËÈ ÔÓËÒ͇ Ô·ÚÙÓÏ˚ ÍÓ΢ÂÒÚ‚ÂÌÌÓ ÓˆÂÌË‚‡Î‡Ò¸ Ò ÔÓÏÓ˘¸˛ ÌÓ‚Ó„Ó Ô‡‡ÏÂÚ‡ – ÔÓ͇Á‡ÚÂÎfl ÔflÏËÁÌ˚ Ú‡ÂÍÚÓËË. ǂ‰ÂÌË ÔÓ͇Á‡ÚÂÎfl “Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl” ÔÓÁ‚ÓÎËÎÓ ‚˚‰ÂÎËÚ¸ ÔÂËÓ‰˚ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ӊ ‚ Ó·˘ÂÏ Î‡ÚÂÌÚÌÓÏ ÔÂËÓ‰Â Û ÊË‚ÓÚÌ˚ı ÔÓÒΠ‚‚‰ÂÌËfl AF64A, ÍÓÚÓ˚ “Û·Ë‡Î” 17β-˝ÒÚ‡‰ËÓÎ ‚ ÓÚ΢ˠÓÚ J-861. çÓ‚˚ ԇ‡ÏÂÚ˚ (ÓÒÓ·ÂÌÌÓ ÔÓ͇Á‡ÚÂθ ÔflÏËÁÌ˚ Ú‡ÂÍÚÓËË) ÔÓÁ‚ÓÎfl˛Ú ‰ËÒÍËÏËÌËÓ‚‡Ú¸ ÒÔÓÒÓ·ÌÓÒÚ¸ Í Ó·Û˜ÂÌ˲ ÓÚ ÒÌËÊÂÌËfl ÔÓ‰‚ËÊÌÓÒÚË, ‚ ÚÓÏ ˜ËÒÎÂ Ë ‚˚Á˚‚‡ÂÏÓÈ ËÒÒΉÛÂÏ˚ÏË ÔÂÔ‡‡Ú‡ÏË, ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡. äβ˜Â‚˚ ÒÎÓ‚‡: ‚Ó‰Ì˚È ÚÂÒÚ åÓËÒ‡, Ó·Û˜ÂÌËÂ, Ô‡ÏflÚ¸, ˝ÒÚÓ„ÂÌ˚.

àÒÒΉӂ‡ÌË ‚ÎËflÌËfl ÒÚÂÓˉÌ˚ı „ÓÏÓÌÓ‚ ̇ ÙÛÌ͈ËË ÏÓÁ„‡ Ô‰ÒÚ‡‚ÎflÂÚ ÚÂÓÂÚ˘ÂÒÍËÈ Ë Ô‡ÍÚ˘ÂÒÍËÈ ËÌÚÂÂÒ. Ç ˜‡ÒÚÌÓÒÚË, 17β-˝ÒÚ‡‰ËÓÎ (17β-ù) ӷ·‰‡ÂÚ ÌÂÈÓÚÓÙ˘ÂÒÍËÏ Ë ÌÂÈÓÔÓÚÂÍÚÓÌ˚Ï ‰ÂÈÒÚ‚ËÂÏ [8], ÛÎÛ˜¯‡ÂÚ Ó·Û˜ÂÌËÂ Û Î‡·Ó‡ÚÓÌ˚ı ÊË‚ÓÚÌ˚ı ÔË Û„ÌÂÚÂÌËË ˝ÌÂ„ÂÚ˘ÂÒÍÓ„Ó Ó·ÏÂ̇ ‚ ÏÓÁ„ [16] Ë ÔÓÒΠ˯ÂÏ˘ÂÒÍËı ÔÓ‚ÂʉÂÌËÈ [7]. 17β-ù ÍÓÏÔÂÌÒËÛÂÚ Ì‡Û¯ÂÌË ԇÏflÚË ÔË ËÌ„Ë·ËÓ‚‡ÌËË ‡ˆÂÚËÎıÓÎËÌÓ‚˚ı ˆÂÔÚÓÓ‚ ÒÍÓÔÓ·ÏËÌÓÏ [9, 12]. ÖÒÚÂÒÚ‚ÂÌÌÓ ÛÏÂ̸¯ÂÌË ˝ÒÚÓ„ÂÌÓ‚ ‚ ÔÓÒÚÏÂÌÓÔ‡ÛÁÌ˚È ÔÂËÓ‰ ‡ÒÒχÚË‚‡ÂÚÒfl Í‡Í Ù‡ÍÚÓ ËÒ͇ Á‡·Ó΂‡ÂÏÓÒÚ¸˛ ‰ÂÏÂ̈ËÂÈ ‡Î¸ˆ„ÂÈÏÂÓ‚ÒÍÓ„Ó ÚËÔ‡ [13], ÍÓÚÓ‡fl ı‡‡ÍÚÂËÁÛÂÚÒfl ÒÌËÊÂÌËÂÏ ÍÓ„ÌËÚË‚Ì˚ı ÙÛÌ͈ËÈ Ë ÌÂÈӉ„ÂÌÂ‡ÚË‚Ì˚ÏË ÔÓˆÂÒÒ‡ÏË ‚ Û˜‡ÒÚ͇ı ÏÓÁ„‡, ÒÓ‰Âʇ˘Ëı ‚ ÓÒÌÓ‚ÌÓÏ ıÓÎËÌÂ„˘ÂÒÍË ÌÂÈÓÌ˚ Ë Ëı ‡ÍÒÓÌ˚. çÂÓ‰ÌÓÍ‡ÚÌÓ ÔÓ͇Á‡ÌÓ, ˜ÚÓ ‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚˚ (‚/Ê) ËÌ˙Â͈ËË ıÓÎËÌÓÚÓÍÒË̇ 1-˝ÚËÎ-1-(2-„ˉÓÍÒË˝ÚËÎ) ‡ÁËˉËÌËÛχ (AF64A) ‚ ‰ÓÁ 1–3 ÏÍ„/Ï„ ‚˚Á˚‚‡˛Ú Á̇˜ËÚÂθÌÓ ıÓÌ˘ÂÒÍÓ ÒÌËÊÂÌË ÒÓ‰ÂʇÌËfl ‡ˆÂÚËÎıÓÎËÌÓ‚˚ı χÍÂÓ‚ ‚ ÍÓ ÏÓÁ„‡ Ë „ËÔÔÓ͇ÏÔ Í˚Ò Ë Ì‡Û¯ÂÌË ӷۘ‡ÂÏÓÒÚË ÊË‚ÓÚÌ˚ı ‚ ‡Á΢Ì˚ı ÚÂÒÚ‡ı, ÔÓ˝ÚÓÏÛ Â„Ó ÔËÏÂÌfl˛Ú ‰Îfl ÏÓ‰ÂÎËÓ‚‡ÌËfl ‰ÂÏÂ̈ËË ‡Î¸ˆ„ÂÈÏÂÓ‚ÒÍÓ„Ó ÚËÔ‡ [4,

10, 17, 25]. Ç Ô‰˚‰Û˘ÂÏ ËÒÒΉӂ‡ÌËË Ì‡ÏË ·˚ÎÓ ÔÓ͇Á‡ÌÓ ÛÎÛ˜¯ÂÌË ‚˚‡·ÓÚÍË ÛÒÎÓ‚ÌÓ„Ó ÂÙÎÂÍÒ‡ ‡ÍÚË‚ÌÓ„Ó ËÁ·Â„‡ÌËfl Û Í‡ÒÚËÓ‚‡ÌÌ˚ı Í˚Ò, ÔÓÎÛ˜‡‚¯Ëı ÒËÒÚÂÏÌ˚ ËÌ˙Â͈ËË 17β-ù Ë Â„Ó ËÁÓÏÂ‡ 17α-˝ÒÚ‡‰ËÓ· (17α-ù) ‰Ó Ë ÔÓÒΠ‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚ÓÈ ËÌ˙Â͈ËË AF64Ä [2]. Ç Ì‡ÒÚÓfl˘ÂÈ ‡·ÓÚ ·˚ÎÓ ËÒÒΉӂ‡ÌÓ ‚ÎËflÌË AF64A ̇ ÔÓÒÚ‡ÌÒÚ‚ÂÌÌÛ˛ ÓËÂÌÚ‡ˆË˛ ͇ÒÚËÓ‚‡ÌÌ˚ı Í˚Ò ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡. è‰ÔÓ·„‡ÂÚÒfl, ˜ÚÓ ‚Ó‰Ì˚È ÚÂÒÚ Ì‡Ë·ÓΠ‡‰ÂÍ‚‡ÚÌÓ ÓÚ‡Ê‡ÂÚ Ì‡Û¯ÂÌËfl ‚ „ËÔÔÓ͇ÏÔÂ, ‚ ÚÓÏ ˜ËÒÎÂ Ë ÓÔÓÒ‰ӂ‡ÌÌ˚ ıÓÎËÌÂ„˘ÂÒÍËÏ ‰ÂÙˈËÚÓÏ [5, 18]. àÁ‚ÂÒÚÌÓ, ˜ÚÓ AF64Ä ˜ÂÂÁ ÌÂÒÍÓθÍÓ ‰ÌÂÈ ÔÓÒΠ‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚˚ı ËÌ˙Â͈ËÈ ÛÒËÎË‚‡ÂÚ ÔËÁ̇ÍË Ô‡ÒÒË‚ÌÓ„Ó Ôӂ‰ÂÌËfl Û Í˚Ò [1]. Ç Ò‚Ó˛ Ó˜Â‰¸ ÒÌËÊÂÌË „ÓÏÓ̇θÌÓ„Ó ÙÓ̇ Û Í˚Ò ÔÛÚÂÏ Í‡ÒÚ‡ˆËË ÒÔÓÒÓ·ÒÚ‚ÛÂÚ ÛÒËÎÂÌ˲ ‰ÂÔÂÒÒË‚Ì˚ı ÒÓÒÚÓflÌËÈ [21]. èË Ù‡χÍÓÎӄ˘ÂÒÍËı ËÒÒΉӂ‡ÌËflı Ôӂ‰ÂÌË Í˚Ò ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡ ÏÓÊÂÚ ÓÚ‡Ê‡Ú¸ Ë ‰Û„Ë ˝ÙÙÂÍÚ˚ ‚¢ÂÒÚ‚, χÒÍËÛ˛˘Ë ӷۘÂÌË Í˚Ò Ì‡ıÓʉÂÌ˲ Ì‚ˉËÏÓÈ Ô·ÚÙÓÏ˚ [5]. èÓ˝ÚÓÏÛ ÌÂÓ·ıÓ‰ËÏÓ ·˚ÎÓ Û˜ËÚ˚‚‡Ú¸, ˜ÚÓ Ë AF64Ä, Ë ‡ÁÌÓ ÒÓ‰ÂʇÌË „ÓÏÓÌÓ‚ Û Í˚Ò ÏÓ„ÛÚ ‚ÎËflÚ¸ ̇ ·ÚÂÌÚÌ˚È ÔÂËÓ‰

208

ÇÎËflÌË ˝ÒÚÓ„ÂÌÓ‚ ̇ Ó·Û˜ÂÌË Í˚Ò

209

퇷Îˈ‡ 1. àÁÏÂÌÂÌË ‚ÂÒ‡ „ÓÏÓ̘ۂÒÚ‚ËÚÂθÌ˚ı Ó„‡ÌÓ‚ ͇ÒÚËÓ‚‡ÌÌ˚ı Í˚Ò ÔÓÒΠÒËÒÚÂÏÌ˚ı ËÌ˙Â͈ËÈ 0.2 Ï„/Í„ 17β-˝ÒÚ‡‰ËÓ· Ë J-861 (M ± SE; % ÓÚ Á̇˜ÂÌËÈ ‰Îfl ÍÓÌÚÓÎfl) é„‡Ì èÓÒÚ‡Ú‡ ëÂÏÂÌÌ˚ ÔÛÁ˚¸ÍË ç‡‰ÔӘ˜ÌËÍË íËÏÛÒ ëÂÎÂÁÂÌ͇

äÓÌÚÓθ: AF64A + ‡ÒÚ‚ÓËÚÂθ; ëåÜ + ‡ÒÚ‚ÓËÚÂθ; n = 10 n = 10 100.0 ± 6.3 100.0 ± 6.5 100.0 ± 6.3 100.0 ± 5.9 100.0 ± 7.0

106.4 ± 4.9 114.5 ± 6.7 106.2 ± 4.5 88.4 ± 5.1 105.0 ± 7.3

AF64A + 0.2 Ï„/Í„ 17β-˝ÒÚ‡‰ËÓÎ; n = 10

AF64A + 0.2 Ï„/Í„ J-861; n = 10

138.1 ± 7.2*## 119.5 ± 5.4# 130.1 ± 3.6*## 83.9 ± 4.7# 117.5 ± 8.5

112.3 ± 4.5 111.0 ± 4.9 107.3 ± 3.5 99.0 ± 8.0 115.0 ± 4.5

èËϘ‡ÌËÂ. á̇˜ÂÌËfl ‚ÂÒ‡ Ó„‡ÌÓ‚ ‰‡Ì˚ ‚ ‡Ò˜ÂÚ ̇ 100 „ χÒÒ˚ Ú· Í˚Ò ÔÓÒΠ˝ÍÒÔÂËÏÂÌÚ‡; n – ˜ËÒÎÓ Í˚Ò ‚ ͇ʉÓÈ „ÛÔÔÂ. ÑÓÒÚÓ‚ÂÌÓÒÚË ‡Á΢ËÈ (ÔÓ ÍËÚÂ˲ ëÚ¸˛‰ÂÌÚ‡): # – p < 0.05, ## – p < 0.001 ÔÓ ÓÚÌÓ¯ÂÌ˲ Í ÍÓÌÚÓθÌÓÈ „ÛÔÔÂ; * – p < 0.001 ÔÓ ÓÚÌÓ¯ÂÌ˲ Í „ÛÔÔÂ, ÔÓÎÛ˜‡‚¯ÂÈ AF64A (‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚Ó ‚‚‰ÂÌËÂ) + ‡ÒÚ‚ÓËÚÂθ (per os).

̇ıÓʉÂÌËfl Ô·ÚÙÓÏ˚ (ãè) ˜ÂÂÁ Ì ҂flÁ‡ÌÌ˚Â Ò ÔÓÒÚ‡ÌÒÚ‚ÂÌÌÓÈ ÓËÂÌÚ‡ˆËÂÈ ÏÂı‡ÌËÁÏ˚ ‚ÓÁ‰ÂÈÒÚ‚Ëfl ̇ ÏÓÁ„. ÑÎfl ËÒÒΉӂ‡ÌËfl ‰ÂÈÒÚ‚Ëfl 17β-ù Ë ÒËÌÚÂÚ˘ÂÒÍÓ„Ó ÒÚÂÂÓËÁÓÏÂ‡ 17α-ù – ÔÂÔ‡‡Ú‡ J-861 – ̇ Ó·Û˜ÂÌË Í˚Ò ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡ ·˚Î ÔËÏÂÌÂÌ ‡Á‡·ÓÚ‡ÌÌ˚È Ì‡ÏË ÌÓ‚˚È ÔÓ„‡ÏÏÌ˚È ÍÓÏÔÎÂÍÒ “Behavioral Vision”, ÔÓÁ‚ÓÎfl˛˘ËÈ ‡ÒÒ˜ËÚ˚‚‡Ú¸ ̇fl‰Û Ò Ó·˘ÂÔËÌflÚ˚ÏË ÔÓ͇Á‡ÚÂÎflÏË (ãè, ‰ÎË̇ Ú‡ÂÍÚÓËË, ÒÍÓÓÒÚ¸ ‰‚ËÊÂÌËfl, ÒÛÏχÌÓ ‡ÒÒÚÓflÌË ‰Ó Ô·ÚÙÓÏ˚ Ë Ú.‰.) ‚ÂÏfl ‡͈ËÈ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ÔÓ‚ÂıÌÓÒÚË ‚Ó‰˚ Ë ÒÚÂÔÂ̸ ÔË·ÎËÊÂÌËfl Ú‡ÂÍÚÓËË ÔÓËÒ͇ Ô·ÚÙÓÏ˚ Í ÓÔÚËχθÌÓÈ [19]. ñÂθ˛ ̇ÒÚÓfl˘ÂÈ ‡·ÓÚ˚ ·˚ÎÓ ËÁÛ˜ÂÌË ‰ÂÈÒÚ‚Ëfl ÒËÒÚÂÏÌÓ„Ó ‚‚‰ÂÌËfl 17β-ù Ë J-861 ̇ Ó·Û˜ÂÌË Í˚Ò Ò ıÓÌ˘ÂÒÍËÏ ÒÌËÊÂÌËÂÏ ıÓÎËÌÂ„˘ÂÒÍËı ÙÛÌ͈ËÈ, ‚˚Á‚‡ÌÌ˚Ï ‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚˚ÏË ËÌ˙Â͈ËflÏË AF64A ̇ ÙÓÌ ÒÌËÊÂÌËfl ÒÓ‰ÂʇÌËfl ÒÓ·ÒÚ‚ÂÌÌ˚ı „ÓÏÓÌÓ‚ ÔÓÒΠ͇ÒÚ‡ˆËË, ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡. åÖíéÑàäÄ ê‡·ÓÚÛ ÔÓ‚Ó‰ËÎË ‚ ÁËÏÌËÈ ÔÂËÓ‰ ̇ Í˚Ò‡ı҇ψ‡ı ÎËÌËË ÇËÒÚ‡ χÒÒÓÈ 200–230 „ ËÁ ÔËÚÓÏÌË͇ “ëÚÓηӂ‡fl”. ÜË‚ÓÚÌ˚ı ÒÓ‰ÂʇÎË ‚ Òڇ̉‡ÚÌ˚ı ÛÒÎÓ‚Ëflı ‚Ë‚‡Ëfl ÔÓ Ó‰ÌÓÏÛ ‚ ÍÎÂÚÍ ÔË Ò‚Ó·Ó‰ÌÓÏ ‰ÓÒÚÛÔÂ Í ‚Ó‰Â Ë ÔˢÂ. èÓÒΠ10-‰Ì‚ÌÓ„Ó Í‡‡ÌÚË̇ ÓÚ·‡ÍÓ‚˚‚‡ÎË Í˚Ò, Ì ÔË·‡‚Ë‚¯Ëı ‚ ‚ÂÒÂ. ÑÎfl ÒÌËÊÂÌËfl Ë ‚˚‡‚ÌË‚‡ÌËfl ÒÓ‰ÂʇÌËfl ÒÓ·ÒÚ‚ÂÌÌ˚ı „ÓÏÓÌÓ‚ Í˚Ò Í‡ÒÚËÓ‚‡ÎË ÔÓ‰ ˝ÙËÌ˚Ï Ì‡ÍÓÁÓÏ, ̇ ÒÎÂ‰Û˛˘ËÈ ‰Â̸ ÙÓÏËÓ‚‡ÎË ˜ÂÚ˚ „ÛÔÔ˚, Á‡ÚÂÏ ‚ Ú˜ÂÌË 7 ‰ÌÂÈ ÊË‚ÓÚÌ˚Ï ‰‚Ûı ÔÓ‰ÓÔ˚ÚÌ˚ı „ÛÔÔ Âʉ̂ÌÓ ÔÂÓ‡Î¸ÌÓ ‚‚Ó‰ËÎË 0.2 Ï„/Í„ 17β-ù (“Sigma”, ëòÄ) ËÎË J-861 (“Jenafarm”, ÉÂχÌËfl) ‚ 0.2-0.27 ÏΠχÒÎflÌÓ„Ó ‡ÒÚ‚Ó‡; Í˚Ò˚ ‰‚Ûı ÍÓÌÚÓθÌ˚ı „ÛÔÔ ÔÓÎÛ˜‡ÎË Ï‡ÒÎflÌ˚È ‡ÒÚ‚Ó. AF64Ä „ÓÚÓ‚ËÎË ËÁ AF64 (“Bachem”, ÉÂχÌËfl) ÔÂ‰ ËÌ˙Â͈ËflÏË ÔÓ ÏÂÚÓ‰Û î˯Â‡ [10] Ë ‡Á‚Ó‰ËÎË ËÒÍÛÒÒÚ‚ÂÌÌÓÈ ÒÔËÌÌÓÏÓÁ„Ó‚ÓÈ ÊˉÍÓÒÚ¸˛ (ëåÜ). óÂÂÁ 7 ‰ÌÂÈ ÔÓÒΠ͇ÒÚ‡ˆËË ÔÓ‰ ˝ÙËÌ˚Ï Ì‡ÍÓÁÓÏ ‚ ÒÚÂÂÓ-

Ú‡ÍÒËÒ Í˚Ò‡Ï ‰‚Ûı ÔÓ‰ÓÔ˚ÚÌ˚ı Ë Ó‰ÌÓÈ ÍÓÌÚÓθÌÓÈ „ÛÔÔ˚ ‚ ·ÓÍÓ‚˚ ÊÂÎÛ‰Ó˜ÍË ÏÓÁ„‡ ËÌ˙ˆËÓ‚‡ÎË 3 ÌÏÓθ/3 ÏÍÎ AF64Ä, ÊË‚ÓÚÌ˚Ï ‰Û„ÓÈ ÍÓÌÚÓθÌÓÈ „ÛÔÔ˚ ËÌ˙ˆËÓ‚‡ÎË 3 ÏÍÎ ëåÜ. Ç ‰‡Î¸ÌÂȯÂÏ ÍÓÌÚÓθÌÓÈ Ì‡Á˚‚‡ÎË „ÛÔÔÛ Í˚Ò Ò ‚‚‰ÂÌËÂÏ ëåÜ, ÊË‚ÓÚÌ˚ı Ò ‚‚‰ÂÌËÂÏ AF64A – „ÛÔÔÓÈ “AF64A”, ‡ ÊË‚ÓÚÌ˚ı Ò ‚‚‰ÂÌËÂÏ AF64A, ÔÓÎÛ˜‡‚¯Ëı ËÒÒΉÛÂÏ˚ ‚¢ÂÒÚ‚‡, – “17β-ù” Ë “J-861” ÒÓÓÚ‚ÂÚÒÚ‚ÂÌÌÓ. óÂÂÁ 10 ‰ÌÂÈ ÔÓÒΠËÌ˙Â͈ËË ÄF64Ä Í˚Ò Ó·Û˜‡ÎË Ì‡ıÓʉÂÌ˲ Ì‚ˉËÏÓÈ Ô·ÚÙÓÏ˚ (Íۄ·fl ÔÎÓ˘‡‰Í‡ ‰Ë‡ÏÂÚÓÏ 10 ÒÏ) ‚ ·‡ÒÒÂÈÌ ‰Ë‡ÏÂÚÓÏ 180 ÒÏ ÔÓ Òڇ̉‡ÚÌÓÈ ÒıÂÏ ӷۘ‡˛˘Â„Ó ÚÂÒÚ‡ åÓËÒ‡ [15, 18], ‰‡‚‡fl ËÏ ÔÓ ‰‚ ÔÓÔ˚ÚÍË ‚ ‰Â̸ ˜ÂÂÁ 10 ÏËÌ Ò ‰‚Ûı ‡ÁÌ˚ı ÔÓÁˈËÈ. Ç 1-È ‰Â̸ ÊË‚ÓÚÌÓÏÛ Ô‰ÓÒÚ‡‚ÎflÎË 120 Ò ‰Îfl ̇ıÓʉÂÌËfl Ô·ÚÙÓÏ˚, ‚ ÔÓÒÎÂ‰Û˛˘Ë ‰ÌË – 60 Ò. ä˚Ò‡, Ì ̇¯Â‰¯‡fl Ô·ÚÙÓÏÛ Á‡ Û͇Á‡ÌÌÓ ‚ÂÏfl, ÔÓÏ¢‡Î‡Ò¸ ̇ Ì ˝ÍÒÔÂËÏÂÌÚ‡ÚÓÓÏ Ì‡ 3–5 Ò. ǂ‰ÂÌË ËÒÒΉÛÂÏ˚ı ‚¢ÂÒÚ‚ ÔÓ‰ÓÎʇÎË ‚ Ú˜ÂÌË ‚ÒÂ„Ó ˝ÍÒÔÂËÏÂÌÚ‡, ‚ ‰ÌË Ó·Û˜ÂÌËfl ‚¢ÂÒÚ‚‡ ‚‚Ó‰ËÎË ˜ÂÂÁ 1– 1.5 ˜ ÔÓÒΠÁ‡ÔÎ˚‚Ó‚. ãè ̇ıÓʉÂÌËfl Ô·ÚÙÓÏ˚ Û˜ËÚ˚‚‡ÎË Í‡Ê‰˚È ‰Â̸, ̇ 5-È Ë 10-È ‰Â̸ Ó·Û˜ÂÌËfl ÔÓ‚Ó‰ËÎË ‚ˉÂÓÒ˙ÂÏÍÛ Ë ÍÓÏÔ¸˛ÚÂÌ˚È ‡Ì‡ÎËÁ Ò ÔÓÏÓ˘¸˛ ‡ÔÔ‡‡ÚÌÓ-ÔÓ„‡ÏÏÌÓ„Ó ÍÓÏÔÎÂÍÒ‡ "Behavioral Vision” [19]. ê„ËÒÚËÓ‚‡ÎË ÒÎÂ‰Û˛˘Ë ԇ‡ÏÂÚ˚: 1) ÌÓ‚˚È ÔÓ͇Á‡ÚÂθ ÔflÏËÁÌ˚ Ú‡ÂÍÚÓËË, ı‡‡ÍÚÂËÁÛ˛˘ËÈ ·ÎËÁÓÒÚ¸ Ú‡ÂÍÚÓËË Í ÓÔÚËχθÌÓÈ Ë ‡ÒÒ˜ËÚ˚‚‡ÂÏ˚È Í‡Í ÓÚÌÓ¯ÂÌË ‰ÎËÌ˚ Ú‡ÂÍÚÓËË Í ‰ÎËÌ ‚ÂÍÚÓ‡, Ò‚flÁ˚‚‡˛˘Â„Ó ÏÂÒÚÓ Á‡ÔÛÒ͇ Ò ˆÂÌÚÓÏ Ô·ÚÙÓÏ˚; 2) ÔÓ͇Á‡ÚÂθ “Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl”, ı‡‡ÍÚÂËÁÛ˛˘ËÈ ÌÂÔÓ‰‚ËÊÌÓÒÚ¸ ̇ ‚Ó‰Â Ë ‡ÒÒ˜ËÚ˚‚‡ÂÏ˚È Í‡Í ‚ÂÏfl, ÔÓ‚Ó‰ËÏÓ ÊË‚ÓÚÌ˚Ï ‚ ÌÂÔÓ‰‚ËÊÌÓÏ ÒÓÒÚÓflÌËË (ÒÓ ÒÍÓÓÒÚ¸˛ ÌËÊ ÔÓÓ„Ó‚ÓÈ), ‚ ÔÓˆÂÌÚ‡ı ÓÚÌÓÒËÚÂθÌÓ Â„Ó ãè; Á̇˜ÂÌË ÔÓÓ„‡ ÒÍÓÓÒÚË ·˚ÎÓ ‚˚·‡ÌÓ ˝ÍÒÔÂËÏÂÌڇθÌÓ ‡‚Ì˚Ï 1 ÒÏ/Ò. êÂÁÛθڇÚ˚ Ô‰ÒÚ‡‚ÎflÎË ‚ ‚ˉÂ: Ò‰Ì Á̇˜ÂÌË ± Òڇ̉‡Ú̇fl ӯ˷͇ Ò‰ÌÂ„Ó (M ± SE) ‰Îfl Í‡Ê‰Ó„Ó ÔÓ͇Á‡ÚÂÎfl. èÓ ÓÍÓ̘‡ÌËË ˝ÍÒÔÂËÏÂÌÚ‡ Í˚Ò ‰Â͇ÔËÚËÓ‚‡ÎË, ‚˚‰ÂÎflÎË ‚ÌÛÚÂÌÌË „ÓÏÓ̘ۂÒÚ‚ËÚÂθÌ˚ Ó„‡Ì˚ Ë ‚Á‚¯˂‡ÎË. éˆÂÌÍÛ ‰ÓÒÚÓ-

6 ÜìêçÄã ÇõëòÖâ çÖêÇçéâ ÑÖüíÖãúçéëíà      ÚÓÏ 53      ‹ 2      2003

ÏÛıË̇ Ë ‰.

210

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2

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ÔÓÎÓÊÂÌË Ì‚ˉËÏÓÈ Ô·ÚÙÓÏ˚

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ÔÓÁˈËË Á‡ÔÛÒ͇

êËÒ. 1. ëÓ‚ÓÍÛÔÌÓÒÚ¸ Ú‡ÂÍÚÓËÈ, ÔÓÎÛ˜ÂÌÌ˚ı Ò ÔÓÏÓ˘¸˛ ‡ÔÔ‡‡ÚÌÓ-ÔÓ„‡ÏÏÌÓ„Ó ÍÓÏÔÎÂÍÒ‡ “Behavioral Vision” ̇ 10-È ‰Â̸ Ó·Û˜ÂÌËfl (ÔË Á‡ÔÛÒÍÂ Ò ‰‚Ûı ÔÓÁˈËÈ) ‰Îfl Í˚Ò Í‡Ê‰ÓÈ „ÛÔÔ˚ ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡. ä‡Ê‰˚È ÍÛ„ Ô‰ÒÚ‡‚ÎflÂÚ ÒÓ·ÓÈ Ì‡ÎÓÊÂÌË Ú‡ÂÍÚÓËÈ ‰‚ËÊÂÌËfl Í˚Ò ÒÓÓÚ‚ÂÚÒÚ‚Û˛˘ÂÈ „ÛÔÔ˚: Ä – ÍÓÌÚÓθ: ëåÜ + ‡ÒÚ‚ÓËÚÂθ, n = 10; Å – AF64A + ‡ÒÚ‚ÓËÚÂθ, n = 10; Ç – AF64A + 17β-˝ÒÚ‡‰ËÓÎ, n = 10; É – AF64A + J-861, n = 10; n – ˜ËÒÎÓ Í˚Ò ‚ ͇ʉÓÈ „ÛÔÔÂ; 1 Ë 2 – ÌÓÏÂ‡ ÔÓÁˈËÈ Á‡ÔÛÒ͇.

‚ÂÌÓÒÚË ÂÁÛθڇÚÓ‚ ÔÓ‚Ó‰ËÎË ÔÓ ÍËÚÂ˲ ëÚ¸˛‰ÂÌÚ‡, ‡ Ú‡ÍÊÂ Ò ËÒÔÓθÁÓ‚‡ÌËÂÏ ‰ËÒÔÂÒËÓÌÌÓ„Ó ‡Ì‡ÎËÁ‡ (ANOVA) Ë ÔÓÒÎÂ‰Û˛˘ËÏ Ò‡‚ÌÂÌËÂÏ ÔÓ ÍËÚÂ˲ 縲ÏÂ̇-äÂÈÎÒ‡. êÖáìãúíÄíõ àëëãÖÑéÇÄçàâ чÌÌ˚ ‚Á‚¯˂‡ÌËfl ‚ÌÛÚÂÌÌËı „ÓÏÓÌÁ‡‚ËÒËÏ˚ı ÊÂÎÂÁ ͇ÒÚËÓ‚‡ÌÌ˚ı Í˚Ò ÔË ÒËÒÚÂÏÌÓÏ ÔÂÓ‡Î¸ÌÓÏ ‚‚‰ÂÌËË 17β-ù ‚ ‰ÓÁ 0.2 Ï„/Í„ ·˚ÎË ·ÎËÁÍË ÔÓ Á̇˜ÂÌËflÏ ‰‡ÌÌ˚Ï ÔÓ ËÁÏÂÌÂÌ˲ ‚ÂÒ‡ Ó„‡ÌÓ‚ ÔË ÔÓ‰ÍÓÊÌ˚ı ËÌ˙Â͈Ëflı χÎ˚ı ‰ÓÁ [2]. ǂ‰ÂÌË 17β-ù ÔË‚Ó‰ËÎÓ Í Û‚Â΢ÂÌ˲ ‚ÂÒ‡ ÔÓÒÚ‡Ú˚, ÒÂÏÂÌÌ˚ı ÔÛÁ˚¸ÍÓ‚, ̇‰ÔӘ˜ÌËÍÓ‚ Ë ÛÏÂ̸¯ÂÌ˲ ‚ÂÒ‡ ÚËÏÛÒ‡ (Ú‡·Î. 1). ǂ‰ÂÌË J-861 Ì ‚ÎËflÎÓ Ì‡ ‚ÂÒ „ÓÏÓ̘ۂÒÚ‚ËÚÂθÌ˚ı ÊÂÎÂÁ. ç‡ 5-È ‰Â̸ Ó·Û˜ÂÌËfl ÏÂÊ‰Û Í˚Ò‡ÏË ‡ÁÌ˚ı „ÛÔÔ Ô‡ÍÚ˘ÂÒÍË Ì ·˚ÎÓ ‰ÓÒÚÓ‚ÂÌ˚ı ‡Á΢ËÈ, Á‡ ËÒÍβ˜ÂÌËÂÏ „ÛÔÔ˚ “17β-ù”; Í 10-ÏÛ ‰Ì˛ ÊË‚ÓÚÌ˚ ‚ÒÂı „ÛÔÔ Ó·Û˜ËÎËÒ¸ ̇ıÓ‰ËÚ¸ Ô·ÚÙÓÏÛ (ËÒ. 1, ËÒ. 2). Ç ÔÂ‚ÓÈ ÔÓÔ˚ÚÍ ̇ 10-È ‰Â̸ ÔÓ ÔÓ͇Á‡ÚÂβ ãè ̇ıÓʉÂÌËfl Ô·ÚÙÓÏ˚ ÊË‚ÓÚÌ˚ ‚ÒÂı „ÛÔÔ ·˚ÒÚ ̇ıÓ‰ËÎË Ô·ÚÙÓÏÛ ÔÓ Ò‡‚ÌÂÌ˲ Ò „ÛÔÔÓÈ “AF64A” (ËÒ. 2, Ä), Ë Ò‰ÌËÈ ãè ‰Îfl ÍÓÌÚÓθÌ˚ı ÊË‚ÓÚÌ˚ı ÒÓ‚Ô‡‰‡Î ÔÓ Á̇˜ÂÌ˲ Ò ‡Ì‡Îӄ˘Ì˚Ï ‰Îfl ÌÂ͇ÒÚËÓ‚‡ÌÌ˚ı Í˚Ò ‚ Ô‰˚‰Û˘Ëı ˝ÍÒÔÂËÏÂÌÚ‡ı [4]. ÇÓ ‚ÚÓÓÈ ÔÓÔ˚ÚÍ ãè ÛÏÂ̸¯ËÎÒfl ‰Îfl ‚ÒÂı „ÛÔÔ Í˚Ò (ËÒ. 2, Ä), Ë Ú‡ÂÍÚÓËË ÔÓËÒ͇ ‚ „ÛÔÔÂ

“AF64A” ‚˚„Îfl‰ÂÎË ·ÓΠ̇Ô‡‚ÎÂÌÌÓ ÔÓ Ò‡‚ÌÂÌ˲ Ò ÔÂ‚ÓÈ ÔÓÔ˚ÚÍÓÈ (ËÒ. 1), Ӊ̇ÍÓ ÊË‚ÓÚÌ˚ „ÛÔÔ˚ “J-861" Ì ÔÓ͇Á‡ÎË ‰ÓÒÚÓ‚ÂÌ˚ı ÓÚ΢ËÈ ÓÚ „ÛÔÔ˚ "AF64A”. èÓ˜ÚË Û ÔÓÎÓ‚ËÌ˚ Í˚Ò „ÛÔÔ “AF64A” Ë “J-861" ̇·Î˛‰‡ÎË ÔÂËÓ‰˚ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ÔÓ‚ÂıÌÓÒÚË ‚Ó‰˚ (Ú‡·Î. 2), ÍÓÚÓ˚Â Ë ÏÓ„ÎË ·˚Ú¸ Ô˘ËÌÓÈ ·Óθ¯Ó„Ó Á̇˜ÂÌËfl ãè Ë ÌËÁÍÓ„Ó Á̇˜ÂÌËfl Ò‰ÌÂÈ ÒÍÓÓÒÚË (ËÒ.2, Ä, Å). ì˜ÂÚ ‰ÎËÚÂθÌÓÒÚË ÔÂËÓ‰Ó‚ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ò ÔÓÏÓ˘¸˛ ÔÓ͇Á‡ÚÂÎfl "Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl” ÔÓÁ‚ÓÎËÎ ÓˆÂÌËÚ¸ Ëı ÍÓ΢ÂÒÚ‚ÂÌÌÓ (Ú‡·Î. 2). Ç ÔÂ‚˚ ‰ÌË ˝ÍÒÔÂËÏÂÌÚ‡ Ò‰ÌË Á̇˜ÂÌËfl ÔÓ͇Á‡ÚÂÎfl “Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl” ‰Îfl ͇ʉÓÈ „ÛÔÔ˚ Í˚Ò ÒÛ˘ÂÒÚ‚ÂÌÌÓ ÏÂÌflÎËÒ¸ ‚ Á‡‚ËÒËÏÓÒÚË ÓÚ ‰Ìfl Ó·Û˜ÂÌËfl Ë ÔÓÔ˚ÚÍË (Ú‡·Î. 2, 5-È ‰Â̸). Ç „ÛÔÔ‡ı Í˚Ò “AF64A” Ë “J-861" ˜ËÒÎÓ ÊË‚ÓÚÌ˚ı Ò Ú‡ÍËÏË ÔÓfl‚ÎÂÌËflÏË ·˚ÎÓ ·Óθ¯ËÏ Ë Ô‡ÍÚ˘ÂÒÍË Ì ËÁÏÂÌËÎÓÒ¸ Ò 5-„Ó ÔÓ 10-È ‰Â̸ ˝ÍÒÔÂËÏÂÌÚ‡, Í ÚÓÏÛ ÊÂ Û ˝ÚËı ÊË‚ÓÚÌ˚ı ‚ÂÏfl Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl ‚ÓÁÓÒÎÓ. ǂ‰ÂÌË 17β-ù ÛÏÂ̸¯ËÎÓ ˜ËÒÎÓ Í˚Ò Ò ÔÓfl‚ÎÂÌËflÏË ÔÂËÓ‰Ó‚ ÌÂÔÓ‰‚ËÊÌÓÒÚË, ‚˚Á˚‚‡ÂÏ˚ı AF64A (Ú‡·Î. 2). èË Ì‡Î˘ËË ‰ÎËÚÂθÌ˚ı ÔÂËÓ‰Ó‚ ÌÂÔÓ‰‚ËÊÌÓÒÚË ÔÓ˜ÚË Û ÔÓÎÓ‚ËÌ˚ Í˚Ò (Ú‡·Î. 2) Ò‰Ìflfl ÒÍÓÓÒÚ¸ ̇ıÓʉÂÌËfl Ô·ÚÙÓÏ˚ ‚ „ÛÔÔ‡ı "AF64A” Ë “J-861" ·˚· ‰ÓÒÚ‡ÚÓ˜ÌÓ ‚˚ÒÓ͇ ÔÓ Ò‡‚ÌÂÌ˲ Ò Ú‡ÍÓ‚ÓÈ ‚ ÍÓÌÚÓθÌÓÈ „ÛÔÔ (ËÒ.2, Å), ˜ÚÓ „Ó‚ÓËÚ Ó ·˚ÒÚÓÚ ‰‚ËÊÂÌËÈ ÓÒڇθÌ˚ı ÊË‚ÓÚÌ˚ı ‚ ˝ÚËı „ÛÔÔ‡ı Ë ÓÚÒÛÚÒÚ‚ËË Ó·˘ÂÈ Ô‡ÒÒË‚ÌÓÒÚË.

ÜìêçÄã ÇõëòÖâ çÖêÇçéâ ÑÖüíÖãúçéëíà      ÚÓÏ 53      ‹ 2      2003

ÇÎËflÌË ˝ÒÚÓ„ÂÌÓ‚ ̇ Ó·Û˜ÂÌË Í˚Ò èÂ‚‡fl ÔÓÔ˚Ú͇ (ÔÓÁˈËfl 1)

50 40 *

30

*

30 20

ÇÚÓ‡fl ÔÓÔ˚Ú͇ (ÔÓÁˈËfl 2)

Ä

50 40

**

20

**

10

10

0

0 Å 30

30

211

*

*

*

*

20

20

10

10

0

0 Ç

8

8

6

6

4

4 *

* *

2 0

5-È ‰Â̸ 10-È ‰Â̸ ÍÓÌÚÓθ: ëåÜ + + ‡ÒÚ‚ÓËÚÂθ AF64A + 17β-ù

2 0

5-È ‰Â̸ 10-È ‰Â̸ AF64A + + ‡ÒÚ‚ÓËÚÂθ AF64A + J-861

êËÒ. 2. ÇÎËflÌË ÒËÒÚÂÏÌ˚ı per os ‚‚‰ÂÌËÈ 17β-˝ÒÚ‡‰ËÓ· Ë J-861 ̇ ÔÓËÒÍ Ô·ÚÙÓÏ˚ ͇ÒÚËÓ‚‡ÌÌ˚ÏË Í˚Ò‡ÏË Ò ‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚ÓÈ ËÌ˙Â͈ËÂÈ ıÓÎËÌÓÚÓÍÒË̇ AF64A. Ä – ãè, Ò; Å – ÒÍÓÓÒÚ¸, ÒÏ/Ò; Ç – ÔflÏËÁ̇ Ú‡ÂÍÚÓËË ÔË Ó·Û˜ÂÌËË ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡. чÌÌ˚ Ô‰ÒÚ‡‚ÎÂÌ˚ Í‡Í M ± SE; ‰ÓÒÚÓ‚ÂÌÓÒÚË ‡Á΢ËÈ (ANOVA Ò ÔÓÒÎÂ‰Û˛˘ËÏ Ò‡‚ÌÂÌËÂÏ ÔÓ ÍËÚÂ˲ 縲ÏÂ̇-äÂÈÎÒ‡) : * – p < 0.05, ** – p < 0.01 ÔÓ ÓÚÌÓ¯ÂÌ˲ Í „ÛÔÔÂ, ÔÓÎÛ˜‡‚¯ÂÈ ‚/Ê AF64A + per os ‡ÒÚ‚ÓËÚÂθ.

îÓχ Ú‡ÂÍÚÓËÈ Ë Ëı ÔÎÓÚÌÓÒÚ¸ ‚ ÔÂ‚ÓÈ ÔÓÔ˚ÚÍ (ËÒ. 1) ÔÓ͇Á˚‚‡˛Ú ‰ÓÒÚ‡ÚÓ˜ÌÓ ı‡ÓÚ˘Ì˚È ÔÓËÒÍ Ô·ÚÙÓÏ˚ Û Í˚Ò „ÛÔÔ˚ “AF64A” Ë ·ÓΠ‚˚‡ÊÂÌÌÛ˛ ̇Ô‡‚ÎÂÌÌÓÒÚ¸ ‰‚ËÊÂÌËfl ‚ ÒÂÍÚÓ Ò Ô·ÚÙÓÏÓÈ Û Í˚Ò ÓÒڇθÌ˚ı „ÛÔÔ. Ç˚˜ËÒÎÂÌÌ˚È Ì‡ ÓÒÌÓ‚‡ÌËË ‰‡ÌÌ˚ı ÔÓ Ú‡ÂÍÚÓËË ÔÓ͇Á‡ÚÂθ ̇Ô‡‚ÎÂÌÌÓÒÚË ÔÓËÒ͇ ÍÓ΢ÂÒÚ‚ÂÌÌÓ ÓÚ‡Ê‡Î ‡Á΢Ëfl ‚ Ó·Û˜ÂÌÌÓÒÚË Í˚Ò ÍÓÌÚÓθÌÓÈ „ÛÔÔ˚ Ë „ÛÔÔ˚ “J-861" ÔÓ Ò‡‚ÌÂÌ˲ Ò „ÛÔÔÓÈ "AF64A” ÔÓ ˆÂÎÂÛÒÚÂÏÎÂÌÌÓÒÚË ÔÓËÒ͇, ÌÂÁ‡‚ËÒËÏÓ ÓÚ ÔÂËÓ‰Ó‚ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ӊ (ËÒ. 2, Ç, 10-È ‰Â̸). èÓ͇Á‡ÚÂθ ̇Ô‡‚ÎÂÌÌÓ-

ÒÚË ÔÓËÒ͇ ‚ ÔÂ‚ÓÈ ÔÓÔ˚ÚÍ ‰ÓÒÚÓ‚ÂÌ ÓÔËÒ˚‚‡ÂÚ ÒÚÂÔÂ̸ Ó·Û˜ÂÌÌÓÒÚË Í˚Ò, ˜ÂÏ ãè, ÌÓ ‚Ó ‚ÚÓÓÈ ÔÓÔ˚ÚÍÂ, „‰Â ·Óθ¯ËÌÒÚ‚Ó Ú‡ÂÍÚÓËÈ ‚Ó ‚ÒÂı „ÛÔÔ‡ı Í˚Ò ¯ÎÓ Í Ô·ÚÙÓÏ ÔÓ˜ÚË ÔÓ ÔflÏÓÈ, ‰ÓÒÚÓ‚ÂÌÓÒÚ¸ ‡Á΢ËÈ ÏÂÊ‰Û „ÛÔÔ‡ÏË ÛÏÂ̸¯Ë·Ҹ. ÇÚÓÛ˛ ÔÓÔ˚ÚÍÛ „ÛÔÔ‡ Í˚Ò “AF64A” ‚˚ÔÓÎÌË· ÎÛ˜¯Â ‚ 1.7 ‡Á‡ ÔÓ ÔÓ͇Á‡ÚÂβ ãè, ˜ÂÏ ÔÂ‚Û˛, ÌÓ ˝ÚÓ ‚ ÌÂÍÓÚÓÓÈ ÒÚÂÔÂÌË Í‡ÊÛ˘ÂÂÒfl ÛÎÛ˜¯ÂÌËÂ, Ú‡Í Í‡Í ‡ÒÒÚÓflÌË ÔÓ ÔflÏÓÈ ÏÂÊ‰Û ÏÂÒÚÓÏ Á‡ÔÛÒ͇ Ò 1-È ÔÓÁˈËË Ë Ô·ÚÙÓÏÓÈ (135 ÒÏ) ‚ 1.35 ‡Á‡ ·Óθ¯Â, ˜ÂÏ ‡ÒÒÚÓflÌË ÏÂÊ‰Û ÏÂÒÚÓÏ Á‡ÔÛÒ͇ ÒÓ 2-È ÔÓÁˈËË Ë

ÜìêçÄã ÇõëòÖâ çÖêÇçéâ ÑÖüíÖãúçéëíà      ÚÓÏ 53      ‹ 2      2003

6*

ÏÛıË̇ Ë ‰.

212

퇷Îˈ‡ 2. éˆÂÌ͇ ˝ÔËÁÓ‰Ó‚ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ӊ ÔÓ ˜ËÒÎÛ Í˚Ò ‚ „ÛÔÔ (n), ‰Îfl ÍÓÚÓ˚ı ̇·Î˛‰‡ÎËÒ¸ ÔÂËÓ‰˚ ÌÂÔÓ‰‚ËÊÌÓÒÚË, Ë Ò‰ÌÂÏÛ Á̇˜ÂÌ˲ ‡ÒÒ˜ËÚ‡ÌÌ˚ı ‰Îfl ˝ÚËı ÊË‚ÓÚÌ˚ı ÔÓ͇Á‡ÚÂÎÂÈ “Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl” (èè)

ÉÛÔÔ‡

äÓÌÚÓθ: ëåÜ + ‡ÒÚ‚ÓËÚÂθ AF64A + ‡ÒÚ‚ÓËÚÂθ AF64A + 17β-˝ÒÚ‡‰ËÓÎ AF64A + J-861

5-È ‰Â̸ 10-È ‰Â̸ óËÒÎÓ Í˚Ò ‚ èÂ‚‡fl ÔÓÔ˚Ú͇ ÇÚÓ‡fl ÔÓÔ˚Ú͇ èÂ‚‡fl ÔÓÔ˚Ú͇ ÇÚÓ‡fl ÔÓÔ˚Ú͇ „ÛÔÔ n èè n èè n èè n èè 10 10 10 10

3 5 3 4

15.6 ± 2.7 18.4 ± 3.9 15.3 ± 3.2 33.9 ± 11.8

1 5 1 4

30.3 35.8 ± 10.9 33.5 34.8 ± 8.3

1 4 2 5

17.3 46.2 ± 13.2 35.1 ± 21.9 51.9 ± 13.3

0 4 2 4

0 48.7 ± 12.6 28.1 ± 9.1 43.7 ± 11.4

èËϘ‡ÌËÂ. èè – ‚ÂÏfl (M ± SE), ÔÓ‚Ó‰ËÏÓ ÊË‚ÓÚÌ˚Ï ‚ ÌÂÔÓ‰‚ËÊÌÓÏ ÒÓÒÚÓflÌËË, Ú. Â. ÒÓ ÒÍÓÓÒÚ¸˛ ÌËÊ ÔÓÓ„Ó‚ÓÈ (1 ÒÏ/Ò), % ÓÚÌÓÒËÚÂθÌÓ„Ó ãè ÊË‚ÓÚÌÓ„Ó; “Ô‡ÒÒË‚Ì˚ÏË” Ò˜ËÚ‡ÎË Í˚Ò, ‰Îfl ÍÓÚÓ˚ı èè ÒÓÒÚ‡‚ËÎÓ Ì ÏÂÌ 10% ÓÚ ãè ÔÓËÒ͇ Ô·ÚÙÓÏ˚.

Ô·ÚÙÓÏÓÈ (100 ÒÏ), ‡ Ò‰Ìflfl ÒÍÓÓÒÚ¸ ‰‚ËÊÂÌËfl ÔÓ˜ÚË Ó‰Ë̇ÍÓ‚‡. çÓ ÔÓ ÔÓ͇Á‡ÚÂβ ̇Ô‡‚ÎÂÌÌÓÒÚË, Ì Á‡‚ËÒfl˘ÂÏÛ ÓÚ ÏÂÒÚ‡ Á‡ÔÛÒ͇, Í˚Ò˚ „ÛÔÔ˚ “AF64A” ‚ 1.6 ‡Á‡ ÛÎÛ˜¯ËÎË ‚˚ÔÓÎÌÂÌË ÚÂÒÚ‡ ÔÓ Ò‡‚ÌÂÌ˲ Ò ÔÂ‚ÓÈ ÔÓÔ˚ÚÍÓÈ. ÇÂÏfl Ô·˚‚‡ÌËfl Í˚Ò ‚ ÒÓÒÚÓflÌËË ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ó‰Â Ë ‚ ÔÂ‚ÓÈ, Ë ‚Ó ‚ÚÓÓÈ ÔÓÔ˚ÚÍ ̇ 10-È ‰Â̸ ‰Îfl Í˚Ò „ÛÔÔ˚ “AF64A” Ô‡ÍÚ˘ÂÒÍË Ì ËÁÏÂÌËÎÓÒ¸ (Ú‡·Î. 2), ‡ ÒÛ˘ÂÒÚ‚ÂÌÌ˚ ‡Á΢Ëfl ÏÂÊ‰Û Í˚Ò‡ÏË „ÛÔÔ˚ “AF64A” Ë ÍÓÌÚÓθÌ˚ÏË ÊË‚ÓÚÌ˚ÏË, ‚˚fl‚ÎÂÌÌ˚ ÔÓ Ì‡Ô‡‚ÎÂÌÌÓÒÚË ÔÓËÒ͇ Ô·ÚÙÓÏ˚, ÓÒÓ·ÂÌÌÓ ‚ ÔÂ‚ÓÈ ÔÓÔ˚ÚÍ (ËÒ. 1 Ë ËÒ. 2, Ç, 10-È ‰Â̸, ÔÂ‚‡fl ÔÓÔ˚Ú͇), ÔÓÁ‚ÓÎfl˛Ú Ó‰ÌÓÁ̇˜ÌÓ ÛÚ‚Âʉ‡Ú¸, ˜ÚÓ ‚‚‰ÂÌË AF64A Û‚Â΢˂‡ÂÚ ãè Í‡Í Á‡ Ò˜ÂÚ ÔÂËÓ‰Ó‚ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ó‰Â, Ú‡Í Ë Á‡ Ò˜ÂÚ ÛıÛ‰¯ÂÌËfl ‰Ó΄ӂÂÏÂÌÌÓÈ Ô‡ÏflÚË. ǂ‰ÂÌË 17β-ù Ë J-861 Á̇˜ËÚÂθÌÓ ÛÏÂ̸¯‡ÎÓ ˝ÙÙÂÍÚ AF64A ÔË Ó·Û˜ÂÌËË ‚ ÚÂÒÚ åÓËÒ‡. éÅëìÜÑÖçàÖ êÖáìãúíÄíéÇ 1. çÓ‚˚ Ë̉ÂÍÒ˚ ‰Îfl ÓÔËÒ‡ÌËfl Ôӂ‰ÂÌËfl Í˚Ò ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡ Ä̇ÎËÁ ÔÂ‚˚ı ÂÁÛθڇÚÓ‚ ̇ÒÚÓfl˘Â„Ó ËÒÒΉӂ‡ÌËfl (ËÒ.1 Ë ËÒ. 2, Ä) ÔÓ͇Á‡Î ̉ÓÒÚ‡ÚÓ˜ÌÓÒÚ¸ ÓÒÌÓ‚ÌÓ„Ó ÔÓ͇Á‡ÚÂÎfl Ó·Û˜ÂÌËfl ÊË‚ÓÚÌ˚ı ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡ – ãè ÓÚ˚Ò͇ÌËfl Ô·ÚÙÓÏ˚ – ‰Îfl ÓÔËÒ‡ÌËfl ÒÎÓÊÌÓ„Ó Ôӂ‰ÂÌËfl ÊË‚ÓÚÌ˚ı ÔË ‰ÂÈÒÚ‚ËË ÌÂÒÍÓθÍËı Ù‡ÍÚÓÓ‚: ıÓÎËÌÂ„˘ÂÒÍÓ„Ó ‰ÂÙˈËÚ‡ ‚ ÏÓÁ„Â, ÒÌËÊÂÌËfl „ÓÏÓ̇θÌÓ„Ó ÙÓ̇, ËÌ˙Â͈ËÈ ˝ÒÚÓ„ÂÌÓ‚. èÓ˝ÚÓÏÛ ·˚ÎË ËÒÔÓθÁÓ‚‡Ì˚ ÌÓ‚˚ Ë̉ÂÍÒ˚: ÔÓ͇Á‡ÚÂÎË Ì‡Ô‡‚ÎÂÌÌÓÒÚË ÔÓËÒ͇ Ë “Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl”. èÓÏËÏÓ ‚ÂÏÂÌË Ì‡ıÓʉÂÌËfl Ô·ÚÙÓÏ˚ ‰Îfl ‡Ì‡ÎËÁ‡ ‚ÎËflÌËfl ËÒÒΉÛÂÏ˚ı ÒÓ‰ËÌÂÌËÈ Ì‡ ÒÔÓÒÓ·ÌÓÒÚ¸ Í˚Ò Í Ó·Û˜ÂÌ˲ ‡ÁÌ˚ÏË „ÛÔÔ‡ÏË ËÒÒΉӂ‡ÚÂÎÂÈ ËÒÔÓθÁÛÂÚÒfl fl‰ Ô‡‡ÏÂÚÓ‚: ‰ÎË̇ Ú‡ÂÍÚÓËË [23], ÒÛÏχÌÓ ‡ÒÒÚÓflÌË ‰Ó Ô·ÚÙÓÏ˚ [6, 11, 23], ˜ËÒÎÓ Ú‡ÂÍÚÓËÈ ‚ÌÛÚË “ÍÓˉÓ‡”, ÓÒ‚‡fl ÎËÌËfl ÍÓÚÓÓ„Ó ÒÓ‰ËÌflÂÚ ÏÂÒÚÓ Á‡ÔÛÒ͇ Ë ˆÂÌÚ Ô·ÚÙÓÏ˚, ‡ ¯ËË̇ ÒÓÒÚ‡‚-

ÎflÂÚ 10% ÓÚ ‰Ë‡ÏÂÚ‡ ·‡ÒÒÂÈ̇ [5]. çË Ó‰ËÌ ËÁ ÔÂ˜ËÒÎÂÌÌ˚ı Ô‡‡ÏÂÚÓ‚ Ì ‚˚˜ÎÂÌflÂÚ ÔÂËÓ‰˚ ‰ÎËÚÂθÌÓÈ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ó‰Â, ı‡‡ÍÚÂÌ˚ ‰Îfl ··Ó‡ÚÓÌ˚ı „˚ÁÛÌÓ‚ ‚ ·‡ÒÒÂÈÌÂ. àÁÏÂÌÂÌË Ò‰ÌÂÈ ÒÍÓÓÒÚË Ô·‚‡ÌËfl Ì ÓÚ‡Ê‡ÂÚ ÒÛÚ¸ ˝ÚÓ„Ó ÔÓˆÂÒÒ‡ Ë ‚ ̇ÒÚÓfl˘ÂÏ ˝ÍÒÔÂËÏÂÌÚ ‚‚Ó‰ËÚ ‚ Á‡·ÎÛʉÂÌËÂ, Á‡ÒÚ‡‚Îflfl Ô‰ÔÓ·„‡Ú¸ ÒÌËÊÂÌË ‡ÍÚË‚ÌÓÒÚË ‚ÒÂı ÊË‚ÓÚÌ˚ı (ËÒ. 2, Å). ǂ‰ÂÌÌ˚È ÔÓ͇Á‡ÚÂθ ÔflÏËÁÌ˚ Ú‡ÂÍÚÓËË ‰‡ÂÚ ·ÓΠ̇„Îfl‰ÌÓÂ, ˜ÂÏ ‰ÎË̇ Ú‡ÂÍÚÓËË, Ô‰ÒÚ‡‚ÎÂÌËÂ Ó ÒÔÓÒÓ·ÌÓÒÚË ÊË‚ÓÚÌÓ„Ó Ì‡ıÓ‰ËÚ¸ Ô·ÚÙÓÏÛ, ÍÓ΢ÂÒÚ‚ÂÌÌÛ˛ ÓˆÂÌÍÛ Ë ÔÓÁ‚ÓÎflÂÚ Ò‡‚ÌË‚‡Ú¸ ÒÚÂÔÂ̸ Ó·Û˜ÂÌÌÓÒÚË ÔÓ Á̇˜ÂÌËflÏ Ì‡Ô‡‚ÎÂÌÌÓÒÚË Ú‡ÂÍÚÓËÈ, ÔÓÎÛ˜ÂÌÌ˚ı ÔË Á‡ÔÛÒÍÂ Ò ‡ÁÌ˚ı ÔÓÁˈËÈ. äÓÏ ÚÓ„Ó, ˝ÚÓÚ ÔÓ͇Á‡ÚÂθ Ì Á‡‚ËÒËÚ ÓÚ ‡ÁÏÂÓ‚ ·‡ÒÒÂÈ̇ Ë ÏÓÊÂÚ ËÒÔÓθÁÓ‚‡Ú¸Òfl ‰Îfl Ò‡‚ÌÂÌËÈ ÂÁÛθڇÚÓ‚, ÔÓÎÛ˜ÂÌÌ˚ı ‡ÁÌ˚ÏË ËÒÒΉӂ‡ÚÂÎflÏË. 2. ÑÂÈÒÚ‚Ë ËÁÏÂÌÂÌËfl „ÓÏÓ̇θÌÓ„Ó ÙÓ̇ Ë ıÓÎËÌÂ„˘ÂÒÍÓ„Ó ‰ÂÙˈËÚ‡ ‚ ÏÓÁ„ ̇ Ó·Û˜ÂÌËÂ Ç ÔËÏÂÌÂÌÌÓÈ Ì‡ÏË ÒıÂÏ ÚÂÒÚ‡ åÓËÒ‡ Ó·˚˜ÌÓ ËÁÛ˜‡ÂÚÒfl ‚ÓÁ‰ÂÈÒÚ‚Ë ‡Á΢Ì˚ı Ù‡ÍÚÓÓ‚ ̇ Ó·Û˜ÂÌËÂ, ‚‚‰ÂÌË ‚¢ÂÒÚ‚ ˜ÂÂÁ 1–1.5 ˜ ÔÓÒΠÚÂÌËÓ‚ÍË ÔÓ‰‡ÁÛÏ‚‡ÂÚ ËÒÒΉӂ‡ÌË Ëı ‰ÂÈÒÚ‚Ëfl ̇ ÔÓˆÂÒÒ ÍÓÌÒÓÎˉ‡ˆËË. é‰Ì‡ÍÓ Ô‰¯ÂÒÚ‚Û˛˘Â ËÌ˙Â͈ËË AF64A ËÁÏÂÌÂÌË „ÓÏÓ̇θÌÓ„Ó ÙÓ̇ ÏÓ„ÎÓ ‚ÎËflÚ¸ ̇ ÌÂÈӉ„ÂÌÂ‡ÚË‚Ì˚ ÔÓˆÂÒÒ˚, ‚˚Á˚‚‡ÂÏ˚ ıÓÎËÌÓÚÓÍÒËÌÓÏ, ˜ÚÓ ‚ÔÓÒΉÒÚ‚ËË ÏÓ„ÎÓ Ò͇Á‡Ú¸Òfl ̇ Ó·Û˜ÂÌËË. Ç Ô‰˚‰Û˘Ëı ‡·ÓÚ‡ı ÔÓ͇Á‡ÌÓ, ˜ÚÓ ÒËÒÚÂÏÌ˚ı ËÌ˙Â͈ËÈ 17β-ù ‰Ó ÔÓ‚Âʉ‡˛˘Â„Ó ÏÓÁ„ ‚ÓÁ‰ÂÈÒÚ‚Ëfl ·˚ÎÓ ‰ÓÒÚ‡ÚÓ˜ÌÓ ‰Îfl ÔÓÒÎÂ‰Û˛˘Â„Ó ÛÎÛ˜¯ÂÌËfl Ó·Û˜ÂÌËfl ÊË‚ÓÚÌ˚ı [24]. ÖÒÚ¸ ‰‡ÌÌ˚Â Ë Ó· ÛÎÛ˜¯‡˛˘ÂÏ ‰ÂÈÒÚ‚ËË ÔÓÒÚÚÂÌËÓ‚Ó˜Ì˚ı ËÌ˙Â͈ËÈ 17β-ù ̇ ‚˚ÔÓÎÌÂÌË ÚÂÒÚ‡ Ó‚‡Ë˝ÍÚÓÏËÓ‚‡ÌÌ˚ÏË Í˚Ò‡ÏË Ì‡ ÒÎÂ‰Û˛˘ËÈ ‰Â̸ [20]. ëÎÓÊÌÓÒÚ¸ Ôӂ‰ÂÌËfl ̇ÒÚÓfl˘Â„Ó ˝ÍÒÔÂËÏÂÌÚ‡ Ô‰ÔÓ·„‡Î‡ χÍÒËχθÌÓ ÔË·ÎËÊÂÌËÂ Í ‰ÂÏÂ̈ËË ‡Î¸ˆ„ÂÈÏÂÓ‚ÒÍÓ„Ó ÚËÔ‡, ˜ÚÓ ÓÔ‡‚‰˚‚‡ÂÚ ÔËÏÂÌÂÌË ‚ÒÂı ‚‡ˇÌÚÓ‚ ËÌ˙Â͈ËÈ ËÒÒΉÛÂÏ˚ı ‚¢ÂÒÚ‚ (‰Ó Ë ÔÓÒΠAF64A, ‡ Ú‡ÍÊ ͇ʉ˚È

ÜìêçÄã ÇõëòÖâ çÖêÇçéâ ÑÖüíÖãúçéëíà      ÚÓÏ 53      ‹ 2      2003

ÇÎËflÌË ˝ÒÚÓ„ÂÌÓ‚ ̇ Ó·Û˜ÂÌË Í˚Ò

‰Â̸ Ó·Û˜ÂÌËfl) ‚ Ó‰ÌÓÏ ÓÔ˚ÚÂ Ë ‚ÓÒÔÓËÁ‚Ӊ˷ ÒËÚÛ‡ˆË˛, ÍÓ„‰‡ ‰Ë‡„ÌÓÁ ÔÓÒÚ‡‚ÎÂÌ Ë Ì‡˜Ë̇ÂÚÒfl ΘÂÌËÂ. 17β-ù ÏÓÊÂÚ Ó͇Á˚‚‡Ú¸ ÌÂÈÓÔÓÚÂÍÚÓÌÓÂ Ë ÌÂÈÓÚÓÙ˘ÂÒÍÓ ‚ÎËflÌË ÔÓ ÌÂÒÍÓθÍËÏ ÏÂı‡ÌËÁχÏ: 1) Í‡Í Í·ÒÒ˘ÂÒÍËÈ ‚ÌÛÚËÍÎÂÚÓ˜Ì˚È ˆÂÔÚÓ, ‰ÂÈÒÚ‚Û˛˘ËÈ Ì‡ Ú‡ÌÒÍËÔˆË˛; 2) Í‡Í ÔÓÒ‰ÌËÍ ÏÂÊ‰Û ‚ÚÓ˘Ì˚ÏË ÏÂÒÒẨÊÂ‡ÏË ‚Ó ‚ÌÛÚËÍÎÂÚÓ˜Ì˚ı ÔÓˆÂÒÒ‡ı; 3) ÔÓ ÏÂı‡ÌËÁχÏ, Á‡Ú‡„Ë‚‡˛˘ËÏ ÏÂÏ·‡ÌÌ˚ ˆÂÔÚÓ˚ Ë ËÓÌÌ˚ ͇̇Î˚ [8]. 17β-ù Ë J-861 ÏÓ„ÎË ÛÎÛ˜¯‡Ú¸ Ó·Û˜ÂÌË Á‡ Ò˜ÂÚ ÌÂÈÓÔÓÚÂÍÚÓÌ˚ı Ò‚ÓÈÒÚ‚ Ë (ËÎË) Á‡ Ò˜ÂÚ ‚ÎËflÌËfl ̇ ÔÓˆÂÒÒ ÍÓÌÒÓÎˉ‡ˆËË. àÁ‚ÂÒÚÌÓ, ˜ÚÓ J-861, Í‡Í Ë 17β-ù, ÔÓfl‚ÎflÂÚ ‡ÌÚËÓÍÒˉ‡ÌÚÌ˚ ҂ÓÈÒÚ‚‡ [22], ÌÂÈÓÔÓÚÂÍÚÓÌÓ ‰ÂÈÒÚ‚Ë ÔÓ ˝ÚÓÏÛ ÚËÔÛ ‡ÍÚË‚ÌÓÒÚË ÏÓÊÂÚ ·˚Ú¸ ̇˷ÓΠ‚‡ÊÌ˚Ï, ÔÓÒÍÓθÍÛ AF64A ‚˚Á˚‚‡ÂÚ ‰ÎËÚÂθÌ˚È ÓÍËÒÎËÚÂθÌ˚È ÒÚÂÒÒ ‚ ÍÓÂ Ë „ËÔÔÓ͇ÏÔ [14]. ÇÂÓflÚÌÓ Ë ÒÔˆËÙ˘ÂÒÍÓ ‰ÂÈÒÚ‚Ë 17β-ù Ë J-861 ̇ Ó·Û˜ÂÌËÂ, ÔÓÒÍÓθÍÛ ˝ÒÚÓ„ÂÌ˚ Ó͇Á˚‚‡˛Ú „ËÓ̇θÌÓ ÒÂÎÂÍÚË‚Ì˚ ‚ÎËflÌËfl, ÍÓÚÓ˚ Á‡‚ËÒflÚ ÓÚ ‰ÓÁ˚ Ë ‚ÂÏÂÌË ‚‚‰ÂÌËfl ˝ÚËı ‚¢ÂÒÚ‚, ̇ ıÓÎËÌÂ„˘ÂÒÍË ÌÂÈÓÌ˚ Ò‰ÌÂ„Ó ÏÓÁ„‡ [12]. åÌÓ„ÓÓ·‡ÁË ÏÂı‡ÌËÁÏÓ‚ „ÓÏÓ̇θÌÓ„Ó ‰ÂÈÒÚ‚Ëfl ̇ ÏÓÁ„, ÔÓ-‚ˉËÏÓÏÛ, ÔÓfl‚ËÎÓÒ¸ Ë ‚ ÒÔÓÒÓ·ÌÓÒÚË 17β-ù ÒÌËʇڸ ˜ËÒÎÓ Í˚Ò Ò ÔÂËÓ‰‡ÏË ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ӊ (Ú‡·Î. 2). Ç Ì‡¯Ëı Ô‰˚‰Û˘Ëı ËÒÒΉӂ‡ÌËflı ÌÂ͇ÒÚËÓ‚‡ÌÌ˚ Í˚Ò˚ ÔË Ó·Û˜ÂÌËË ‚ ÚÂÒÚ åÓËÒ‡ ‰ÂÏÓÌÒÚËÓ‚‡ÎË ÔÂËÓ‰˚ ‰ÎËÚÂθÌÓ„Ó (20–60 Ò) Á‡ÏË‡ÌËfl ̇ ‚Ó‰Â, ÍÓÚÓ˚ ÔÓfl‚ÎflÎËÒ¸ ÔÂËÏÛ˘ÂÒÚ‚ÂÌÌÓ ‚ ÔÂ‚˚ ‰ÌË Ó·Û˜ÂÌËfl. é·˚˜ÌÓ ÂÁÛθڇÚ˚ Ú‡ÍËı ÊË‚ÓÚÌ˚ı Á̇˜ËÚÂθÌÓ Û‚Â΢˂‡ÎË ‡Á·ÓÒ Ò‰ÌËı Á̇˜ÂÌËÈ ãè Ë ÂÒÎË ÓÌË ·˚ÎË ‚ ÔÓÒΉÌËÈ ‰Â̸ Ó·Û˜ÂÌËfl (Ì ·ÓΠ20% ÊË‚ÓÚÌ˚ı), ÚÓ ËÒÍβ˜‡ÎËÒ¸ ÔË ÔÓ‰Ò˜ÂÚ‡ı [4]. Ç Ì‡ÒÚÓfl˘ÂÏ ˝ÍÒÔÂËÏÂÌÚÂ Û ÔÓÎÓ‚ËÌ˚ Í˚Ò „ÛÔÔ “AF64A” Ë “J-861" ̇·Î˛‰‡ÎËÒ¸ ÔÂËÓ‰˚ Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl. èÓ‰Ó·Ì˚ ÔÓ ‚̯ÌËÏ ÔÓfl‚ÎÂÌËflÏ ÔÂËÓ‰˚ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ӊ ı‡‡ÍÚÂÌ˚ ‰Îfl Í˚Ò ÌÂÍÓÚÓ˚ı ÎËÌËÈ, ÓÌË ÔÓfl‚Îfl˛ÚÒfl ‚ ÔÂ‚˚ ‰ÌË Ó·Û˜ÂÌËfl Ë Ò‚Ë‰ÂÚÂθÒÚ‚Û˛Ú Ó Ì‡Û¯ÂÌËË ˝ÏÓˆËÓ̇θÌÓ„Ó ÒÓÒÚÓflÌËfl [3]. Ç ÔÂ‚˚ ‰ÌË Ó·Û˜ÂÌËfl ‚ ̇¯ÂÏ ˝ÍÒÔÂËÏÂÌÚ ̇·Î˛‰‡ÎËÒ¸ Á̇˜ËÚÂθÌ˚ ËÁÏÂÌÂÌËfl ÔÓ͇Á‡ÚÂÎfl "Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl” ‚ ‡ÁÌ˚ı „ÛÔÔ‡ı Í˚Ò, ‚ ÚÓÏ ˜ËÒÎÂ Ë ÏÂÊ‰Û ÔÓÔ˚Ú͇ÏË (Ú‡·Î. 2, 5-È ‰Â̸, ÔÂ‚‡fl Ë ‚ÚÓ‡fl ÔÓÔ˚ÚÍË). ùÚÓ ÏÓÊÌÓ Ò˜ËÚ‡Ú¸ ÔÓfl‚ÎÂÌËÂÏ Û‚Â΢ÂÌËfl ÛÓ‚Ìfl ˝ÏÓˆËÓ̇θÌÓ„Ó Ì‡ÔflÊÂÌËfl Ë ÒÛ·˙ÂÍÚË‚ÌÓÈ ÌÂÓÔ‰ÂÎÂÌÌÓÒÚË Ò‰˚, ˜ÚÓ ÔÓ‰Ú‚Âʉ‡ÂÚÒfl Á̇˜ËÚÂθÌ˚Ï ÒÌËÊÂÌËÂÏ ÔÓ͇Á‡ÚÂÎfl “Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl” Í 10-ÏÛ ‰Ì˛ ‚ „ÛÔÔ “ÍÓÌÚÓθ”. èÓÒÍÓθÍÛ ‚ ̇ÒÚÓfl˘ÂÏ ˝ÍÒÔÂËÏÂÌÚ ˜ËÒÎÓ Í˚Ò Ò ÔÂËÓ‰‡ÏË ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ó‰Â Ë ‰ÎËÚÂθÌÓÒÚ¸ ÔÓÒΉÌËı Ì ÛÏÂ̸¯‡ÎËÒ¸ ‚ Ú˜ÂÌË ‚ÂÏÂÌË Ó·Û˜ÂÌËfl ‚ „ÛÔÔ‡ı “AF64A” Ë “J-861" (Ú‡·Î. 2), Ëı Ô˘ËÌ˚ ÏÓ„ÛÚ ·˚Ú¸ ËÌ˚ÏË. èÓ ÂÁÛÎ¸Ú‡Ú‡Ï Ì‡ÒÚÓfl˘Â„Ó ËÒÒΉӂ‡ÌËfl J-861 ‚ ÓÚ΢ˠÓÚ 17β-ù Ì ‚ÎËflΠ̇ ÔÂËÓ‰˚ Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl Ë Ì ÍÓÏÔÂÌÒËÓ‚‡Î ͇ÒÚ‡ˆËÓÌÌ˚ ËÁÏÂÌÂÌËfl ÔÓ ‰ÂÈÒڂ˲ ̇ ‚ÂÒ „ÓÏÓÌ-

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˜Û‚ÒÚ‚ËÚÂθÌ˚ı ÊÂÎÂÁ (Ú‡·Î. 1), ÔÓ˝ÚÓÏÛ ÏÓÊÌÓ Ô‰ÔÓÎÓÊËÚ¸, ˜ÚÓ Ô‡ÒÒË‚ÌÓ Ô·‚‡ÌË ÓÔÓÒ‰ӂ‡ÌÓ ‰ÂflÚÂθÌÓÒÚ¸˛ „ÓÏÓ̘ۂÒÚ‚ËÚÂθÌ˚ı ‚ÌÛÚÂÌÌËı ÊÂÎÂÁ. èÓ-‚ˉËÏÓÏÛ, Ô˘ËÌÓÈ ÔÓÁ‰ÌËı ÔÂËÓ‰Ó‚ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ӊ ÏÓÊÂÚ ·˚Ú¸ ̉ÓÒÚ‡ÚӘ̇fl ıÓÎËÌÂ„˘ÂÒ͇fl ÙÛÌ͈Ëfl ÏÓÁ„‡, ÛÒÛ„Û·ÎflÂχfl ÒÌËÊÂÌËÂÏ „ÓÏÓ̇θÌÓ„Ó ‚ÎËflÌËfl. çÂÁ‡‚ËÒËÏÓ ÓÚ Ô˘ËÌ ˝ÚÓ„Ó fl‚ÎÂÌËfl Ô‰ÎÓÊÂÌÌ˚È ‚ ‰‡ÌÌÓÈ ‡·ÓÚ ÌÓ‚˚È ÒÔÓÒÓ· ÓˆÂÌÍË Ó·Û˜ÂÌÌÓÒÚË ÊË‚ÓÚÌ˚ı ÔÓ Ì‡Ô‡‚ÎÂÌÌÓÒÚË ÔÓËÒ͇ Ô·ÚÙÓÏ˚ ÔÓÁ‚ÓÎflÂÚ ‚ ÓÚ΢ˠÓÚ ÔËÏÂÌÂÌËfl ãè Ì ۘËÚ˚‚‡Ú¸ ‚ÂÏfl Ô‡ÒÒË‚ÌÓ„Ó Ô·‚‡ÌËfl. ÇõÇéÑõ 1. ëÓ‚ÏÂÒÚÌÓ ‚ÎËflÌË ͇ÒÚ‡ˆËË Ë ˜‡ÒÚ˘ÌÓ„Ó ÒÌËÊÂÌËfl ıÓÎËÌÂ„˘ÂÒÍËı ÙÛÌ͈ËÈ ‚ ñçë, ‚˚Á‚‡ÌÌÓ„Ó ‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚˚Ï ‚‚‰ÂÌËÂÏ AF64A, ÛÏÂ̸¯‡ÎÓ Ó·Û˜‡ÂÏÓÒÚ¸ Ë Û‚Â΢˂‡ÎÓ ˜ËÒÎÓ Ë ‰ÎËÚÂθÌÓÒÚ¸ ÔÂËÓ‰Ó‚ ÌÂÔÓ‰‚ËÊÌÓÒÚË Ì‡ ‚Ó‰Â Û Í˚Ò ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡. 2. ëËÒÚÂÏÌÓ ‚‚‰ÂÌË 17β-˝ÒÚ‡‰ËÓ· Ë ÒËÌÚÂÚ˘ÂÒÍÓ„Ó ÒÚÂÂÓËÁÓÏÂ‡ 17α-˝ÒÚ‡‰ËÓ· (ÔÂÔ‡‡Ú J-861) ÛÎÛ˜¯‡ÎÓ Ó·Û˜ÂÌË ͇ÒÚËÓ‚‡ÌÌ˚ı Í˚Ò Ò ‚ÌÛÚËÊÂÎÛ‰Ó˜ÍÓ‚˚ÏË ËÌ˙Â͈ËflÏË ıÓÎËÌÓÚÓÍÒË̇ ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡. èË ˝ÚÓÏ 17β-˝ÒÚ‡‰ËÓÎ ‚ ÓÚ΢ˠÓÚ J-861 ÛÏÂ̸¯‡Î ˜ËÒÎÓ Ë ‰ÎËÚÂθÌÓÒÚ¸ ÔÂËÓ‰Ó‚ ÌÂÔÓ‰‚ËÊÌÓÒÚË ÊË‚ÓÚÌ˚ı ̇ ‚Ó‰Â. 3. ê‡Á‡·ÓÚ‡Ì ÌÓ‚˚È ÒÔÓÒÓ· ÓˆÂÌÍË ÒÚÂÔÂÌË ÔË·ÎËÊÂÌËfl Ú‡ÂÍÚÓËË Í ÓÔÚËχθÌÓÈ (ÔÓ ÔÓ͇Á‡ÚÂβ ÔflÏËÁÌ˚) Ë ÔÓ͇Á‡Ì‡ ‚‡ÊÌÓÒÚ¸ ‚˚‰ÂÎÂÌËfl “Ô‡ÒÒË‚ÌÓ„Ó ÍÓÏÔÓÌÂÌÚ‡” ̇ ÔËÏÂ ËÒÒΉӂ‡ÌËfl ‰ÂÈÒÚ‚Ëfl AF64A, 17β-˝ÒÚ‡‰ËÓ· Ë J-861 ̇ Ó·Û˜ÂÌË ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡. ꇷÓÚ‡ ‚˚ÔÓÎÌÂ̇ ÔË ÔÓ‰‰ÂÊÍ êÓÒÒËÈÒÍÓ„Ó ÙÓ̉‡ ÙÛ̉‡ÏÂÌڇθÌ˚ı ËÒÒΉӂ‡ÌËÈ (ÔÓÂÍÚ˚ ‹ 00-04-48398 Ë åÄë ‹ 02-04-06599). ëèàëéä ãàíÖêÄíìêõ 1. ÄÈ‡ÔÂÚfl̈ å.É., òÛÈÍËÌ ç.ç., クË̇ à.è. éÒÓ·ÂÌÌÓÒÚË Ôӂ‰ÂÌËfl Í˚Ò, ‚˚Á‚‡ÌÌ˚ ˜‡ÒÚ˘ÌÓÈ ‰Â„ÂÌÂ‡ˆËÂÈ ÌÂÈÓÌÓ‚ „ËÔÔÓ͇ÏÔ‡ // ÜÛÌ. ‚˚Ò¯. ÌÂ‚. ‰ÂflÚ. 1998. í. 48. ‹ 1. ë. 130–134. 2. ãÂÏÓÌÚÓ‚‡ ç.ç., è˙˜Â‚ Ç.ä., ÅÂÁÌÓÒÍÓ Å.ä. Ë ‰. ÇÎËflÌË 17β-˝ÒÚ‡‰ËÓ· Ë Â„Ó ËÁÓÏÂ‡ 17α-˝ÒÚ‡‰ËÓ· ̇ Ó·Û˜ÂÌË Í˚Ò Ò ıÓÌ˘ÂÒÍËÏ ıÓÎËÌÂ„˘ÂÒÍËÏ ‰ÂÙˈËÚÓÏ ‚ ÏÓÁ„ // Å˛Î. ˝ÍÒÔÂËÏ. ·ËÓÎÓ„ËË Ë Ï‰ˈËÌ˚. 2000. í. 129. ‹ 5. ë. 525–527. 3. èÓÌÓχ‚ Ñ.Å., ÇËÌÓ„‡‰Ó‚‡ Ö.è. ë‡‚ÌËÚÂθÌ˚È ‡Ì‡ÎËÁ ÒÔÓÒÓ·ÌÓÒÚË Í Ó·Û˜ÂÌ˲ ‚ ‚Ó‰ÌÓÏ ÚÂÒÚ åÓËÒ‡ Í˚Ò, ‡Á΢‡˛˘ËıÒfl ÔÓ ÒÍÓÓÒÚË ‚˚‡·ÓÚÍË ÛÒÎÓ‚ÌÓ„Ó ÂÙÎÂÍÒ‡ ‡ÍÚË‚ÌÓ„Ó ËÁ·Â„‡ÌËfl // ÜÛÌ. ‚˚Ò¯. ÌÂ‚. ‰ÂflÚ. 2000. í. 50. ‹ 6. ë. 974–981. 4. Bachurin S., Oxenkrug G., Lermontova N. et al. N-Acetylserotonin, Melatonin and Their Derivatives Improve Cognition and Protect against β-Amyloid-Induced Neurotixicity // Ann. N.Y. Acad. Sci. 1999. V. 890. P. 155–166.

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Effects of Estrogens on Learning of Rats with Chronic Brain Cholinergic Deficit in Morris Water Maze T. V. Mukhina, N. N. Lermontova, G. I. Van’kin, M. Öettel, V. K. Patchev, S. O. Bachurin Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow oblast; “Jenafarm”, Jena, Germany A chronic deprivation of brain cholinergic functions in rats caused by intracerebroventricular injection of neurotoxin AF64A increases the escape latency in Morris water maze test as compared to control sham-operated animals. Measurements and analysis of rat movement tracks using an original computerized “Behavioral Vision” system revealed the ability of 17β-Estradiol and its synthetic isomer J-861 (both administered daily in per os dose 0.2 mg/kg during 7 days before and 10 days after a single intracerebroventricular injection of AF64A) to improve learning of the animals. Directivity of search trajectories was estimated by a novel index of track straightness. The introduction of an index of “passive swimming” made it possible to reveal episodes of immobility in water-maze behavior of AF64A-injected animals. Unlike J-861, 17β-Estradiol almost completely eliminated these episodes. The newly developed indices (especially straightness) seem to be very useful in differentiating learning ability of rats from a decrease in their mobility in the Morris water-maze test, in particular, in case of the estrogens under study. Key words: Morris water maze, learning, memory, estrogens. ÜìêçÄã ÇõëòÖâ çÖêÇçéâ ÑÖüíÖãúçéëíà      ÚÓÏ 53      ‹ 2      2003