二甲双胍对2型糖尿病大鼠肠神经GLP-1受体表达的影响

Effects of Metformin on the expression of GLP-1R in the enteric nervous system of type 2diabetic rats

目的研究二甲双胍对2型糖尿病(Type 2diabetes mellitus,T2DM)大鼠肠神经细胞胰高血糖样肽-1受体(Glucagon-like peptide-1receptor,GLP-1R)表达的影响,探讨二甲双胍用药后肠神经GLP-1R的表达变化与血糖的关系。方法雄性Wistar大鼠随机分为3组,每组6只:Wistar正常大鼠组(W-C);T2DM模型对照组(T2DM-C);T2DM二甲双胍组(T2DM-M)。分别测定各组大鼠用药前及用药后第2、8周空腹血糖、空腹血清GLP-1,用药前及用药后8周空腹血清胰岛素。第8周处死各组大鼠,RT-PCR和免疫印迹法(Western blot)测定回肠末端肌间神经丛GLP-1RmRNA和蛋白的水平。结果 T2DM-M组大鼠用药后空腹血糖及空腹血清胰岛素较前显著降低(P<0.01),空腹血清GLP-1较前显著升高(P<0.01),与同时间点T2DM-C组相比差异有统计学意义(P<0.01)。用药后第8周,RT-PCR结果显示GLP-1RmRNA在T2DM-M组肠神经丛表达水平明显高于T2DM-C组GLP-1R mRNA的表达水平(P<0.01)。Western-blot结果显示T2DM-M组肠神经丛GLP-1R蛋白表达水平明显高于T2DM-C组肠神经丛GLP-1R蛋白表达水平(P<0.05)。结论二甲双胍能显著提高T2DM大鼠肠神经GLP-1R的表达,可能在二甲双胍降低2型糖尿病的血糖中发挥了重要作用。

Objective To study the effects of metformin on the expression of Glucagon-like peptidelreceptor （GLP-1R） in the enteric nervous system of type 2 diabetic（T2DM）rats, and to explore the relationship between GLP-1R expression, and blood glucose. Methods Wistar rats were randomly divided into three groups： Wistar control group（W-C）, T2DM control group（T2DM-C）, T2DM Metformin treat group （T2DM-M）, 6 rats in each group. Fasting blood glucose and fast- ing glucagon-like peptide-l（GLP-1） were detected before intragastric administration of metformin and 2 weeks, 8 weeks after intragastric administration of metformin. Fasting insulin in the plasma before intragastric administration of metformin and 8 weeks after intragastric administration of metformin was also detected. After 8 weeks, the rats were sacrificed and the expression of GLP-1R in the enteric nervous was studied by RT-PCR and Western Blot. Results Fasting blood