花旗泽仁对胰岛素抵抗大鼠肝脏CaSR mRNA、蛋白表达及AKT活性的影响

摘要

目的:观察花旗泽仁对胰岛素抵抗(IR)大鼠肝脏组织中钙敏感受体(CaSR) mRNA、蛋白表达及蛋白激酶B(AKT)活性的影响,探讨花旗泽仁改善2型糖尿病胰岛素抵抗的作用机制.方法:雄性Wistar大鼠用复合脂肪乳连续灌胃4周配合小剂量注射链脲佐菌素的方法复制2型糖尿病胰岛素抵抗模型,将大鼠随机分为花旗泽仁组、阳性对照组、模型对照组、空白对照组.检测空腹血糖(FBG)及空腹血清胰岛素(FINS),并计算胰岛素敏感指数(ISI);采用qRT-PCR、Western blot技术检测CaSR mRNA、CaSR蛋白、磷酸化AKT(Ser473和Thr308)蛋白表达水平.结果:与空白对照组比较,模型对照组组大鼠FBG及FINS水平明显增高,ISI显著降低;与模型对照组相比,花旗泽仁组和阳性对照组大鼠FBG和FINS水平明显降低,ISI明显升高;与空白对照组比较,模型对照组大鼠肝脏组织中CaSR mRNA表达水平明显降低;与模型对照组相比,花旗泽仁组和阳性对照组大鼠肝脏组织中CaSR mRNA表达水平显著增高;与空白对照组比较,模型组大鼠肝脏组织中CaSR蛋白、磷酸化AKT(Ser473和Thr308)蛋白表达量均显著降低;与模型对照组相比,花旗泽仁组和阳性对照组大鼠肝脏组织中CaSR 蛋白、磷酸化AKT(Ser473和Thr308)蛋白表达量均明显增加.结论:花旗泽仁可能通过调节CaSR基因及蛋白表达,改善2型糖尿病胰岛素抵抗.%Objective:To observe the influence of Huaqizeren(HQZR) on the expressions of protein CaSR(calcium-sensing receptor),CaSR mRNA,Protein AKT (Kinase B) of the liver tissues in rats with insulin resistance(IR),in order to explore the mechanism of HQZR improving T2DM (Type 2 Diabetes Mellitus) with IR.Methods:The IR model was established with compound fat emulsion diet for four weeks and small-dose STZ injection in male Wistar rats.The rats were randomly divided into the normal control group,the model group,the HQZR group,and the positive control group.FBG(Fasting blood glucose) and FINS(fasting insulin) were tested and ISI (insulin sensitivity index) was calculated.The expressions of CaSR mRNA,protein CaSR and phosphorylated AKT(Ser473 and Thr308) were detected with qRT-PCR and Western blot techniques.Results:In terms of the levels of FBG,FINS,and ISI,FBG and FIN were significantly increased with decreased ISI in the model group,compared to the normal control group after medication;FBG and FINS were significantly decreased with increased ISI in both the HQZR group and the positive control group compared to the normal group.In terms of the expression of CaSR mRNA,it was significantly decreased in the model group compared to the normal control group;it was significantly increased after the treatment in both the HQZR group and the positive control group.In terms of protein expressions of CaSR and phosphorylated AKT,they were decreased after modeling,whereas they were significantly increased after medication both in the HQZR group and in the positive control group.Conclusion:HQZR may improve IR by regulating CaSR mRNA,protein CaSR and AKT.