中枢注射Nesfatin-1与Exendin(9-39)对大鼠摄食和胃肠动力调节的影响

The Influence of Nesfatin-1 and Exendin(9-39) Injected into the Centre on Food Intaking and Gastrointestinal Regulation in Rats

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 influences and mechanisms of intracerebroventricular injection with Exendin （9-39） on the changes of food intake and gastrointestinal dynamics induced by Nesfatin-1 in rats. Methods： Forty Wistar rats were randomly divided into four groups： normal control group （NC）, Nesfatin-1 combined with saline treated group （NS）, Nesfatin-1 combined with Exendin （9-39）treated group （NE）, Exendin （9-39） combined with saline treated group （ES）. All the animals were surgically implanted with indwelling cannulas in the PVN, then Nesfatin-1 or Exendin （9-39） was delivered to the PVN, food and water intake as well as body weight were measured before the injection, the same data were measured at 12 hour and 24 hour after the injection. Gastric emptying was measured by intragastric administration of methyl cellulose-phenol red solution. The expression levels of GLP-1 receptor （GLP-1R） mRNA in the PVN were measured by semi-quantitative RT-PCR. Results： Compared with basal food intake, NS group rats exhibited markedly food intake decrease 12 h, 24 h after injection （P〈0.05）, NE group exhibited food increase compared with NS group（P〈0.05）, but an opposite result compared with NC group 12 h, 24 h after injection（P〈0.05）. NS and NE group showed water intake decrease 12 h, 24 h after injection compared with basal water intake （P〈0.05）. Compared with basal body weight, NS group rats exhibited body weight decrease 12 h, 24 h after injection（P〈0.05）, NE group exhibited body weight decrease 12 h after injection（P〈0.05）, but an opposite result compared with NS group （P〈0.05）; NS group rats exhibited lower gastric emptying compared with NC and NE group after injection （P〈0.05）. The levels ofhypothalamic GLP-1RmRNA were increased compared with NC group （P〈0.05）. Conclusions： GLP-1 receptor antagonist could abate the inhibition of feeding and gastrointestinal motility caused by Nesfatin-1. This result suggested CNS GLP-1 neurons may be a target for the satiety hormone Nesfatin-1. Nesfatin-1 may interact with GLP-1 neurons to involved in feeding and the regulation of gastrointestinal motility.