Ghrelin在情感中枢与胃功能调控作用研究

发布时间：2018-10-18 13:05

【摘要】： 目的:(1)研究ghrelin在海马CA1区对胃运动的影响及机制;(2)阐明ghrelin对胃窦平滑肌细胞钙依赖性钾通道开放的影响和机制;(3)观察海马内外源性ghrlein对大鼠学习记忆的影响。方法:采用核团微量注射药物,记录清醒大鼠胃运动,观察ghrlein对清醒大鼠胃运动的影响和机制;采用急性分离豚鼠胃窦平滑肌细胞和膜片钳技术,探讨ghrelin对胃窦平滑肌细胞钙依赖性钾通道开放的影响机制;海马CA1区微量注射药物,应用跳台和Morris水迷宫实验,探讨海马CA1区内外源性ghrelin对大鼠学习记忆的影响及机制。结果:(1)在体胃运动研究:海马CA1区注入外源性ghrelin可显著增强胃收缩活动(P＜0.01),该作用可被ghrelin受体拮抗剂阻断;L-Arg可显著增强ghrelin对清醒大鼠胃运动的幅度(P＜0.05);相反,L-NAME可逆转ghrelin促进胃运动的作用(P＜0.05)。(2)全细胞膜片钳研究:胃窦平滑肌细胞存在钙依赖性钾通道;ghrelin显著可抑制胃窦平滑肌细胞膜上的钙依赖性钾电流(P＜0.01);L-Arg可使ghrelin对胃窦平滑肌细胞钙依赖性钾电流的抑制作用显著减弱(P＜0.01);而L-NANE使ghrelin该抑制作用加强(P＜0.01)。(3)行为学研究:海马CA1区注射ghrelin可明显增加大鼠学习记忆能力(P＜0.05),ghrelin受体阻断剂[D-Lys(3)]-GHRP-6可消除ghrelin增强大鼠学习记忆作用(P＜0.05);L-NAME可明显减弱ghrelin促进大鼠学习记忆能力(P＜0.05),而ghrelin抗血清可使该作用增强(P＜0.05)。结论:海马CA1区ghrelin均可明显增强大鼠胃运动幅度;Ghrelin可抑制该细胞膜上钙依赖性钾通道的开放;海马CA1区内外源性ghrelin可明显增加大鼠学习记忆能力;上述ghrelin调控作用可能与NO代谢通路有关。
[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.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R341

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