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Ghrelin对C75抑制小鼠胃排空和胃肠通过量的影响及RIY对吗啡镇痛作用的影响

The Interaction between Ghrelin and C75 on Gastric Emptying and Gastrointestinal Transit in Mice and the Influence of RIY on the Antinociceptive Effects of Morphine

【作者】 卢研宇

【导师】 陈强;

【作者基本信息】 兰州大学 , 生理学, 2010, 硕士

【摘要】 C75是脂肪酸合酶(FAS)的抑制剂。脂肪酸合酶是乙酰辅酶A合成脂肪酸过程中的关键酶。C75能抑制脂肪酸合酶的活性。已经有很多文献报道,C75在抑制肿瘤、糖尿病和减肥等都有很好的作用。C75能抑制小鼠的摄食,增加能量代谢的消耗,因此能使小鼠减肥。胃促生长素(Ghrelin)作为C75功能性拮抗剂研究。Ghrelin主要功能有刺激垂体前叶释放生长激素、增加食欲、调节能量平衡、促进胃酸分泌、增强机体免疫力与抗应激能力等作用。由于胃肠运动会对小鼠的摄食产生影响,因此我们的实验目的就是研究C75是否对小鼠的胃排空和胃肠通过量有影响,这种作用是否与Ghrelin相关。采用低压冷冻干燥法测量小鼠的胃排空量,通过营养性碳糊法测量小鼠的胃肠通过量。实验结果表明Ghrelin能明显减弱C75对小鼠胃排空的未通过量的抑制作用。本文的第二部分是研究RIY对吗啡镇痛作用的影响。RIY是从油菜籽中提取的有活性的三肽。已经有人证明,RIY能降低自发性高血压小鼠的血压。还有人报道说,RIY能抑制摄食和胃排空,并且这个作用是通过刺激内源性CCK分泌,通过CCKA受体途径起到作用,CCKA受体拮抗剂氯戊米特能拮抗RIY抑制摄食和胃排空的作用。由于内源性CCK和内源性阿片受体在焦虑,学习记忆和镇痛作用中有相互拮抗的作用,本文研究了RIY是否影响吗啡的镇痛作用。侧脑室给药RIY,5分钟后,皮下给药吗啡,吗啡给药后10min、20min、30min、40min、50min、60min、70min、80min、90min、120min,通过热甩尾法测小鼠的甩尾值。实验结果表明,RIY能剂量依赖的影响吗啡的镇痛作用。高剂量RIY(200nmol/mouse, i. c. v.)在吗啡给药10min时能明显能增强吗啡的镇痛作用,而低剂量RIY(100nmol/mouse, i. c. v.)能抑制吗啡的镇痛作用。

【Abstract】 C75 was synthesed as an inhibitor of fatty acid synhase(FAS).FAS is the key enzyme which catalyzes the condensation of acetyl-CoA and malony-CoA to generate long chain fatty acids in the cytoplam。FAS was inhibited by the C75. It was reported that C75 can inhibit tumor, diabetes and lose weight. C75 can lose weight of mice for it can reduce food intake and increase the energe consumed. Ghrelin was studied as a C75 inhibitor, which can stimulate the growth hormone release, enhance appetite, balance the energe, insicrete the acid and so on. For the food intake and gastrointestinal mobility are closely related, the present study was designed to investigate the effects and mechanisms of C75 on gastric emptying and gastrointestinal transit.The gastric emptying and gastrointestinal transit were measured by lyophilization method and charcoal meal test method, respectively. Our data showed that ghrelin can attenuate the function of C75 to decrease gastrointestinal mobility.In the second section we studied that RIY influenced the antinociceptive effects of morphine. The tripeptide Arg-Ile-Tyr(RIY) was from subtilisin digest of rapeseed protein, which was the residue of rapeseed after extraction of oil. Previous studies indicated that RIY decreased blood pressure after oral administration in spontaneously hypertensive rats(SHR), this tripeptide also inhibited food intake and gastric emptying after peripheral adimnistration in mice via CCKA receptors, and this function of RIY can be inhibited by the CCKA antagonist lorglumide. In this study,we want to found if RIY and morphine have any interaction in the antinociceptive action. RIY was administrative by intracerebroventricular(i.c.v.) before 5min the subcutaneous(s.c) morphine. The latency time was tested by the warm water tail immersion test. after morphine administrative 10min,20min,30min,40min,50min,60min,70min,80min, 90min,120min. The result showed that high dose of RIY(200nmol/mouse,i.c.v.)enhanced the morphine’s antinociceptive after 10min administration morphine, while the low dose of RIY(100nmol/mouse, i.c.v.)can inhibit the morphine’s antinociceptive.

【关键词】 C75Ghrelin胃排空胃肠通过量RIY吗啡镇痛
【Key words】 C75GhrelinGastric emptyingGastrointestinal transitRIYmorphineantinociceptive
  • 【网络出版投稿人】 兰州大学
  • 【网络出版年期】2010年 12期
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