菩人丹超微粉对T2DM大血管损伤大鼠骨骼肌IRS-1,GLUT-4,PI-3K,NF-κB蛋白表达的影响

Effect of Purendan Superfine Powder on IRS-1,PI3K,GLUT4,NF-κB Protein Expression of Skeletal Muscles in Type 2 Diabetic Mellitus Rats with Macroangiopathy

目的:观察菩人丹超微粉(Puren dan superfine powder,PRD)对2型糖尿病(T2DM)大鼠骨骼肌组织胰岛素受体底物1(IRS-1)、磷脂酰肌醇-3激酶(PI3K)、葡萄糖转运蛋白4(GLUT4)、核因子-κB(NF-κB)蛋白表达的影响,探讨PRD调控糖尿病糖脂代谢紊乱,保护大血管内皮损伤的分子机制。方法:采用灌胃脂肪乳结合1次性尾静脉快速注射链脲佐菌素(streptozotocin,STZ,30 mg.kg-1)法复制T2DM模型。低、中、高剂量PRD(0.885,1.770,3.540 g.kg-1)每日ig给药1次,连续给药4周,罗格列酮(0.36×10-3g.kg-1)为阳性对照药。Western blot法测定各组大鼠骨骼肌组织中IRS-1,PI3K,GLUT-4,NF-κB蛋白的表达,并用Quantity One图像分析确定杂交带的吸光度积分值。结果:T2DM大血管病变大鼠骨骼肌组织IRS-1,PI3K,GLUT4蛋白表达与正常对照组比较明显降低(P<0.01),NF-κB蛋白表达显著升高。各组药物治疗后,低、中、高剂量PRD均能显著提高T2DM大鼠骨骼肌组织PI3K的表达,PRD中、高剂量组大鼠骨骼肌IRS-1,GLUT4的蛋白质表达水平明显升高(P<0.01),NF-κB蛋白质表达水平显著降低(P<0.05),阳性对照药罗格列酮也有相应作用。结论:PRD通过促进IRS-1,GLUT4和PI3K蛋白表达,抑制NF-κB蛋白表达,恢复胰岛素信号转导通路,抑制糖尿病状态下的炎症因子表达,从而有效改善胰岛素抵抗,降低血糖、血脂,保护大血管内皮损伤。

Objective：To explore the molecular mechanisms of Purendan superfine powder（PRD）on metabolic disorder and the protection on macroangiopathy by investigating the protein expression of insulin receptor substrate-1（IRS-1）,phosphatidylinositol 3-kinase（PI3K）,glucose transporter 4（GLUT4） and nuclear factor-κB（NF-κB） of skeletal muscles in type 2 diabetes mellitus（T2DM） rats with macroangiopathy.Method： High-fat-diet/streptozotocin（STZ,30 mg · kg-1）-induced type 2 diabetes mellitus rats were developed and treated with PRD（0.885,1.770,3.540 g · kg-1） for four weeks and rosiglitazone（0.36×10-3 g · kg-1） was used as positive control drugs,then western blot assay was used to analyze the protein expression of IRS-1,PI3K,GLUT 4 and NF-κB of skeletal muscle in the rats.Result： The protein expression of IRS-1,PI3K and GLUT-4 was significantly decreased in T2DM group compared with the control group（P＆lt;0.01）,while NF-κB expression was significantly increased（P＆lt;0.01）.After the treatment of PRD,the expression of IRS-1,PI3K and GLUT-4 was up-regulated,and NF-κB was down-regulated significantly（P＆lt;0.05 or P＆lt;0.01）,which was equivalent to the positive drugs.Conclusion： PRD could improve insulin resistance,decrease blood glucose and fat,protect the vascular endothelium injury by up-regulating IRS-1,PI-3K and GLUT 4 protein expression and down-regulating NF-κB protein expression of skeletal muscle in T2DM rats.