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

摘要:

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^-3 g·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。

Abstract:

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<0.01), while NF-κB expression was significantly increased (P<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<0.05 or P<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.