下丘脑室旁核注射GLP-1 对糖尿病大鼠中枢GLP-1 受体表达

目的:探讨下丘脑室旁核(hypothalamic paraventricular nucleus,PVN)注射GLP-1(胰高血糖素样肽-1)对糖尿病大鼠胃排空的影响及机制。方法:30只Wistar大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)和GLP-1干预组(GLP-1组),每组各10只。DM组和GLP-1组腹腔注射链脲佐菌素,三组大鼠均PVN区埋置套管,恢复7d,GLP-1组微量注射0.5μg/0.5μl的GLP-1,NC组和DM组大鼠PVN区微量注射等体积生理盐水。甲基纤维素-酚红灌胃法检测胃排空;半定量RT-PCR检测大鼠下丘脑GLP-1RmRNA的表达。结果:DM组胃排空率较NC组明显升高(P<0.05),GLP-1组胃排空明显低于DM组(P<0.05),GLP-1组和NC组差异无统计学意义(P>0.05)。GLP-1组下丘脑GLP-1RmRNA的表达明显高于DM组和NC组(P<0.05),并与胃排空率成负相关(P<0.05)。DM组和NC组差异无统计学意义(P>0.05)。结论:PVN区注射GLP-1可以抑制糖尿病大鼠早期胃排空加速,作用机制可能和促进下丘脑GLP-1受体表达有关。

Effection of GLP-1 Injection in Paraventricular Nucleus on the Expression of GLP-1 Receptor and Gastric Emptying in Diabetic Rats

Objective: To investigate the effection of GLP-1 injection GLP-1 in paraventricular nucleus on the expression of GLP-1 receptor and gastric emptying in diabetic rats.Methods: Thirty Wistar rats were randomly divided into three groups: Group 1: normal control group(NC group),Group 2: diabetic mellitus group(DM group) and Group 3: GLP-1 treated group(GLP-1 group).All of rats were posited a cannula in PVN,the rats of Group 2 and Group 3 were induced by intraperitoneal injection of streptozotocin(STZ).The rats of Group 3 were injected 0.5μg/0.5μl GLP-1 and isovolumic normal saline for Group 1 and Group 2 in PVN after 7-day recovery period following surgery.Gastric emptying was measured by intragastric administration of methyl cellulose-phenol red solution.The GLP-1 levels in the hypothalamus were measured by EISIA method,the expression levels of GLP-1R mRNA in the hypothalamus were measured by semi-quantitative RT-PCR.Results: The gastric emptying of Group 2 showed significantly accelerated compared with that Group 1(P<0.05).which decreased significantly in Group 3 compared to Group 2(P< 0.05),There was no statistical difference between Group 2 and Group 1(P>0.05).The expression of GLP-1 and GLP-1R mRNA in hypothalamus of Group 3 was increased significantly compared with in the other two groups and no difference between Group 2 and Group 1(P>0.05),which showed a negative correlation with decrease of gastric emptying(P<0.05).Conclusion: GLP-1 Injection in PVN delays acceleration of gastric emptying during the early stage of diabetic rats.The expression of GLP-1 receptor in the hypothalamus is promoted by GLP-1 may be the mechanism.