胰高血糖素样肽-1对糖尿病大鼠胃排空的非受体通路的影响

Influence of Glucagon-like peptide-1 on non-receptors-mediated pathway of gastric emptying in diabetic rats

目的探讨室旁核(Paraventricular nucleus,PVN)内胰高血糖素样肽-1(Glucagon-like pepetide-1,GLP-1)是否存在非受体通路参与糖尿病大鼠胃排空的中枢调节。方法 40只雄性Wistar大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)、GLP-1(7-36)干预组(GLP组)、Exendin(9-39)联合GLP-1干预组(E-G组)及Exendin(9-39)干预组(Exendin组)。制备糖尿病大鼠模型,PVN埋置套管并给予GLP-1(7-36)或Exendin(9-39)等药物,2周后甲基纤维素-酚红溶液测胃排空;实时荧光定量分析法检测PVN区GLP-1受体(GLP-1R)mRNA表达情况。结果注射STZ 2周后,GLP组及E-G组胃排空率较DM组、Exendin组均明显降低(P均<0.05),但高于NC组(P<0.05);GLP组及E-G组的下丘脑GLP-1R mRNA表达较DM组、NC组、Exendin组均明显增高(P均<0.05)。GLP组胃排空率和空腹血糖较E-G组降低(P<0.05);下丘脑GLP-1R mRNA表达GLP组与E-G组比较差异无统计学意义(P>0.05)。结论室旁核注射GLP-1可减缓糖尿病大鼠早期的胃排空,推测GLP-1影响胃排空的中枢作用机制除促进GLP-1受体表达增加外,非受体作用通路亦发挥重要作用。

Objective To explore the non-receptors mediated pathway of Glucagon-like Peptide-1 （ GLP-1 ） injection into paraventricularis nucleus （PYN） on the gastric emptying in diabetic rats. Methods 40 male Wistar rats were ran- domly divided into 5 groups, including normal control group （NC group） , diabetic mellitus group （DM group）, GLP-1 （7-36） treated group （ GLP group）, Exendin （ 9-39 ） combined with GLP-1 （7-36） group （ E-G group）, Exendin （ 9- 39） treated group （Exendin group）. Diabetes model was made, then put cannulas into PVN and administer GLP-1 （7- 36） or Exendin （9-39） to rats through cannulas. Two weeks later, gastric emptying was measured by intragastric admin- istration of methyl cellulose-phenol red solution and the expression levels of GLP-1R mRNA in the hypothalamus were measured by real-time fluorescent quantitative polymerase chain＇ s reac injection, GLP group and E-G group showed lower gastric emptying an and Exendin group （P 〈 0.05 ）, but still higher than NC group （P 〈 0 tion （RT-PCR）. Results After 2 weeks of STZ d fasting blood-glucose compared with DM group .05 ） , the expression levels of GLP-1R mRNA in GLP group and E-G group were significantly higher than those in DM group, NC group and Exendin group （P 〈 0.05）. GLP group showed lower gastric emptying and fasting blood-glucose than E-G group （ P 〈 0.05 ）, the expression levels of GLP-1R mRNA showed no significant difference （P 〉 0.05）. In addition, the expression of GLP-1R in hypothalamus and the gastric emptying showed a negative relation in GLP group and Exendin group, but the expression of GLP-1R in hypothalamus and the gastric emptying in NC group, DM group and E-G group showed no relationship. Conclusion GLP-1 injection into PVN can postpone gastric emptying during the early stage of diabetes, in addition, non-receptor channels maybe exist in the central regulatory mechanisms of gastric emptying other than promoting expression of GLP-1R.