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目的:探讨下丘脑室旁核注射GLP-1R拮抗剂Exendin(9-39)对Nesfatin-1所致大鼠摄食和胃肠动力改变的影响及作用机制。方法:选择40只雄性Wistar大鼠,随机分成正常对照组(NC组)、Nesfatin-1组(NS组)、Exendin(9-39)组(ES组)、Nesfatin-1联合Exendin(9-39)组(NE组)。采用下丘脑室旁核(PVN)埋置套管并分别给予以上药物干预,干预前和干预后的12小时、24小时记录和比较各组大鼠的摄食、饮水及体重变化。2天后,采用甲基纤维素-酚红溶液灌胃法测各组大鼠胃排空率,实时荧光定量法(RT-PCR)检测下丘脑及胃组织GLP-1Rm RNA的表达。结果:与基础摄食量比较,NS组大鼠给药后12 h、24 h的摄食量减少(P<0.05),NE组大鼠给药后12 h、24 h的摄食量减少(P<0.05),但较NS组增加(P<0.05);与基础饮水量比较,NS组、NE组给药后12 h饮水量减少(P<0.05);与基础体重比较,NS组大鼠给药后12 h、24 h的体重降低(P<0.05),NE组大鼠给药后12 h的体重降低(P<0.05),但较NS组增加(P<0.05);NS组大鼠给药后胃排空率较NC、NE组大鼠显著下降(P<0.05),NS组大鼠下丘脑GLP-1Rm RNA的表达量较NC组增加(P<0.05)。结论:中枢给予GLP-1R拮抗剂能减弱Nesfatin-1引起的摄食抑制、胃排空延迟及体重下降效应,Nesfatin-1可能通过与GLP-1的协同作用参与摄食及胃肠动力的调节。
Objective: To investigate the effects of exendin (9-39), a GLP-1R antagonist, injected into the paraventricular nucleus of hypothalamus on food intake and gastrointestinal motility induced by Nesfatin-1 in rats and its mechanism. Methods: Forty male Wistar rats were randomly divided into normal control group (NC group), Nesfatin-1 group (NS group), Exendin (9-39) group (ES group), Nesfatin-1 combined with Exendin ) Group (NE group). The cannula was implanted with paraventricular hypothalamic nucleus (PVN), and the above drug intervention was given. Changes of food intake, drinking water and body weight of rats in each group were recorded and compared at 12 hours and 24 hours after intervention. Two days later, the gastric emptying rate of rats in each group was measured by gavage with methylcellulose-phenol red solution. The expression of GLP-1RmRNA in hypothalamus and stomach tissue was detected by real-time fluorescence quantitative PCR (RT-PCR). Results: Compared with the basic food intake, the food intake of rats in NS group decreased at 12 h and 24 h after administration (P <0.05), but decreased at 12 h and 24 h (P <0.05) ) Compared with the NS group (P <0.05). Compared with the baseline water intake, the water intake of the NS group and the NE group at 12 h after administration decreased (P <0.05). Compared with the basal body weight, (P <0.05). The body weight of rats in NE group decreased 12 h after administration (P <0.05), but increased compared with NS group (P <0.05). After NS administration, The gastric emptying rate was significantly lower than that in NC and NE groups (P <0.05). The expression of GLP-1R mRNA in hypothalamus of NS group was higher than NC group (P <0.05). CONCLUSION: The central administration of GLP-1R antagonist can attenuate the feeding inhibition, delayed gastric emptying and weight loss induced by Nesfatin-1. Nesfatin-1 may participate in the feeding and gastrointestinal motility regulation through the synergistic effect with GLP-1.