【摘要】： 目的:(1)研究ghrelin在海馬CA1區(qū)對胃運動的影響及機制;(2)闡明ghrelin對胃竇平滑肌細(xì)胞鈣依賴性鉀通道開放的影響和機制;(3)觀察海馬內(nèi)外源性ghrlein對大鼠學(xué)習(xí)記憶的影響。 方法:采用核團微量注射藥物,記錄清醒大鼠胃運動,觀察ghrlein對清醒大鼠胃運動的影響和機制;采用急性分離豚鼠胃竇平滑肌細(xì)胞和膜片鉗技術(shù),探討ghrelin對胃竇平滑肌細(xì)胞鈣依賴性鉀通道開放的影響機制;海馬CA1區(qū)微量注射藥物,應(yīng)用跳臺和Morris水迷宮實驗,探討海馬CA1區(qū)內(nèi)外源性ghrelin對大鼠學(xué)習(xí)記憶的影響及機制。 結(jié)果:(1)在體胃運動研究:海馬CA1區(qū)注入外源性ghrelin可顯著增強胃收縮活動(P＜0.01),該作用可被ghrelin受體拮抗劑阻斷;L-Arg可顯著增強ghrelin對清醒大鼠胃運動的幅度(P＜0.05);相反,L-NAME可逆轉(zhuǎn)ghrelin促進胃運動的作用(P＜0.05)。(2)全細(xì)胞膜片鉗研究:胃竇平滑肌細(xì)胞存在鈣依賴性鉀通道;ghrelin顯著可抑制胃竇平滑肌細(xì)胞膜上的鈣依賴性鉀電流(P＜0.01);L-Arg可使ghrelin對胃竇平滑肌細(xì)胞鈣依賴性鉀電流的抑制作用顯著減弱(P＜0.01);而L-NANE使ghrelin該抑制作用加強(P＜0.01)。(3)行為學(xué)研究:海馬CA1區(qū)注射ghrelin可明顯增加大鼠學(xué)習(xí)記憶能力(P＜0.05),ghrelin受體阻斷劑[D-Lys(3)]-GHRP-6可消除ghrelin增強大鼠學(xué)習(xí)記憶作用(P＜0.05);L-NAME可明顯減弱ghrelin促進大鼠學(xué)習(xí)記憶能力(P＜0.05),而ghrelin抗血清可使該作用增強(P＜0.05)。 結(jié)論:海馬CA1區(qū)ghrelin均可明顯增強大鼠胃運動幅度;Ghrelin可抑制該細(xì)胞膜上鈣依賴性鉀通道的開放;海馬CA1區(qū)內(nèi)外源性ghrelin可明顯增加大鼠學(xué)習(xí)記憶能力;上述ghrelin調(diào)控作用可能與NO代謝通路有關(guān)。
[Abstract]:Objective: (1) to study the effect and mechanism of ghrelin on gastric motility in hippocampal CA1 region; (2) to elucidate the effect and mechanism of ghrelin on the opening of calcium-dependent potassium channels in gastric antral smooth muscle cells; (3) to observe the effects of hippocampal ghrlein on learning and memory in rats. Methods: the effects and mechanisms of ghrlein on gastric motility in conscious rats were observed by micronucleus injection, and the gastric smooth muscle cells and patch-clamp technique were used to isolate gastric antral smooth muscle cells from guinea pigs. To investigate the effect of ghrelin on the opening of calcium-dependent potassium channels in gastric antral smooth muscle cells, and to explore the effect and mechanism of exogenous ghrelin in CA1 region of hippocampus on learning and memory in rats by microinjection of drugs into hippocampus CA1. Results: (1) in vivo gastric motility: injection of exogenous ghrelin into CA1 region of hippocampus significantly increased gastric contractile activity (P < 0. 01), which could be blocked by ghrelin receptor antagonist, L-Arg significantly enhanced the amplitude of gastric motility in awake rats (P < 0. 05); on the contrary, it increased the effect of ghrelin on gastric motility in awake rats (P < 0. 05). , L-NAME could reverse the effect of ghrelin on gastric motility (P < 0. 05). (2). The whole cell patch clamp study showed that there were calcium-dependent potassium channels in gastric antral smooth muscle cells, ghrelin significantly inhibited Ca2 +-dependent potassium currents on gastric antral smooth muscle cells (P < 0. 01), and L-Arg induced ghrelin (P < 0. 01). The inhibitory effect of L-NANE on calcium dependent potassium current in gastric antral smooth muscle cells was significantly decreased (P < 0. 01), while that of ghrelin was enhanced by L-NANE (P < 0. 01). (3). The behavioral study showed that injecting ghrelin into CA1 region of hippocampus could significantly increase the ability of learning and memory (P < 0. 05), ghrelin). The receptor blocker [D-Lys (3)]-GHRP-6 could eliminate the effect of ghrelin on enhancing learning and memory in rats (P < 0. 05), L-NAME could significantly reduce the ability of ghrelin to promote learning and memory in rats (P < 0. 05), and ghrelin antiserum could enhance this effect (P < 0. 05). Conclusion: ghrelin in hippocampal CA1 can significantly increase the amplitude of gastric motility in rats, Ghrelin can inhibit the opening of Ca ~ (2 +) -dependent potassium channels on the cell membrane, exogenous ghrelin in the CA1 region of hippocampus can significantly increase the learning and memory ability of rats. The regulation of ghrelin may be related to the metabolic pathway of NO.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2008
【分類號】：R341

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