翻白草总黄酮对2型糖尿病大鼠胰岛素底物-2-磷脂酰肌醇-3激酶信号通路的影响

Effect of Flavonoids from Potentilla discolor on Insulin Substrate -2-Phosphatidylinositol-3 Kinase Signaling Pathway on Type 2 Diabetes Mellitus Rat

摘要:

目的: 研究翻白草总黄酮对2型糖尿病大鼠糖脂代谢和肝组织胰岛素底物-2-磷脂酰肌醇-3激酶(IRS-2-PI3-K)信号通路的影响. 方法: 翻白草经溶剂提取,聚酰胺柱分离提取得总黄酮提取物;以高脂高糖乳剂加链脲佐菌素复制2型糖尿病大鼠模型,将造模成功的大鼠随机分为翻白草总黄酮高剂量(216 mg·kg^﹣1)和低剂量(108 mg·kg^﹣1)、模型对照组、阳性药组(盐酸二甲双胍悬浊液20.8 mg·kg^-1),连续给药4周后,观察其血糖、血脂、游离脂肪酸、肝糖原、胰岛素水平的变化,采用Western blots法检测肝组织IRS-2和PI-3K蛋白的表达. 结果: 与正常组比较,模型组大鼠体重下降、血糖及总胆固醇(TC)升高;高密度脂蛋白胆固醇(HDL-C)下降(P<0.05).与模型组比较,翻白草总黄酮高剂量组血糖下降(P<0.05),TC下降,HDL-C升高(P<0.05);胰岛素和胰岛素抵抗指数均降低(P<0.05);肝组织IRS-2和PI-3K蛋白的表达量升高(P<0.05). 结论: 翻白草总黄酮能纠正2型糖尿病大鼠糖代谢紊乱,可能是通过降低减少肝糖原的输出,提高肝组织胰岛素IRS-2-PI3-K蛋白表达,从而减弱外周胰岛素抵抗.

Abstract:

Objective: To observe the effects of flavonoids from Potentilla discolor (FPD) on insulin substrate-2-phosphatidylinositol-3kinase(IRS-2-PI3K)signaling pathway of liver tissue on type 2 diabetes mellitusmellitus (T2DM) rat. Method: Male Sprague-Dawley(SD) rats were administrated with enriched diet and injected with streptozotocin(STZ,ip,30 mg· kg^-1)to make the model of rat T2DM. The changes of serum fasting blood glucose (FBG),blood lipids,serum fasting insulin (FINS),liver glycogen and free fatty acid were observed. The expressions of IRS-2,PI3-K in liver tissue were determined with Western blots. Result: Compared with normal group, FBG and total cholesterin(TC)were increased,while body weight and high-density lipoprotein cholesterol (HDL-C)were decreased (P<0.05).Compared with model group,FBG, FINS and insulin resistance index in T2DM rats treated with FPDB were decreased significantly(P<0.05).TC were decreased and HDL-C were increased (P<0.05).IRS-2 and PI3-K protein expressions were obviously increased (P<0.05). Conclusion: The effect of FPDB in treating T2DM was probably contributed to adjusting the dyperfunction of glucose and lipid metabolism and associated with its improvement IRS-2--PI3K protein expressions of hepatic insulin on T2DM rat.