基于InsR/PI3K/Akt通路研究岩黄连总碱纠正高脂喂养小鼠糖代谢紊乱的作用机制

Mechanism of Corydalis saxicola total alkaloids on correcting glucose metabolism disorder in high-fat fed mice based on InsR/PI3K/Akt signaling pathway

目的 研究岩黄连Corydalis saxicola总碱对胰岛素抵抗小鼠的影响及作用机制。方法 高脂饮食喂养诱导胰岛素抵抗小鼠,造模成功后给予岩黄连总碱4周,观察岩黄连总碱对胰岛素抵抗小鼠空腹血糖(fasting blood glucose,FBG)、血清胰岛素、口服糖耐量(oral glucose tolerance test,OGTT)、总胆固醇(total cholesterol,TC)、三酰甘油(triacylglycerol,TG)、糖化血清蛋白(glycosylated serum protein,GSP)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、瘦素、脂联素(adiponectin/ADPN,ADP/Acrp30)及肝糖原水平的影响;利用Western blotting检测肝组织中磷酸烯醇式丙酮酸激酶(phosphoenolpyruvate carboxykinase,PEPCK)、叉头框蛋白O1(Forkhead box protein O1,FoxO1)、p-FoxO1、糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)、p-GSK-3β、胰岛素受体(insulin receptor,InsR)、磷脂酰肌醇-3-激酶(phosphatidylinositol-3-kinase,PI3K)、p-PI3K、蛋白激酶B(protein kinase B,Akt)、p-Akt蛋白表达情况。结果 岩黄连总碱可以显著降低胰岛素抵抗指数(P<0.01),改善糖耐量(P<0.01),降低血清中TCH、TG、GSP、LDL-C、瘦素水平(P<0.01),升高HDL-C、ADP/Acrp30水平(P<0.05),促进肝糖原合成(P<0.01),激活InsR/PI3k/Akt通路(P<0.05)。结论 岩黄连总碱可以改善高脂诱导的小鼠胰岛素抵抗,其作用机制可能与激活InsR/PI3K/Akt通路有关。

Objective To study the effect and mechanism of Corydalis saxicola total alkaloids on insulin resistance(IR) mice.Methods Mice were fed with high-fat diet to establish IR model. After IR model on mice was successfully established, C. saxicola total alkaloids was given for four weeks. Effect of C. saxicola total alkaloids on fasting blood glucose(FBG), blood insulin(Ins), oral glucose tolerance(OGTT), total cholesterol(TC), triglyceride(TG), glycosylated serum protein(GSP), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), leptin, adiponectin(ADP/Acrp30) and liver glycogen levels were detected. Western blotting was used to detect expressions of phosphoenolpyruvate kinase(PEPCK), Forkhead box protein O1(FoxO1),p-FoxO1, glycogen synthase kinase-3β(GSK-3β), p-GSK-3β, insulin receptor(InsR), phosphatidylinositol-3-kinase(PI3K), p-PI3K,protein kinase B(Akt) and p-Akt in liver tissue. Results C. saxicola total alkaloids reduced insulin resistance index(P < 0.01),improved oral glucose tolerance(P < 0.01), decreased levels of TC, TG, GSP, LDL-C and leptin in serum(P < 0.01), increased HDLC and ADP/Acrp30 levels(P < 0.05), promoted liver glycogen synthesis(P < 0.01) and activated InsR/PI3K/Akt pathway(P < 0.05).Conclusion C. saxicola total alkaloids can significantly improve insulin resistance induced by high fat fed in mice, and its mechanism may be related to the activation of InsR/PI3K/Akt pathway.