Resveratrol对糖尿病大鼠肾皮质4E-BP1和S6磷酸化表达的影响

目的:探讨Resveratrol对糖尿病(DM)大鼠早期肾脏肥大的影响及其可能的机制?方法:雄性SD大鼠13只,应用链脲佐菌素诱导建立DM大鼠模型,6只正常SD大鼠作为对照(NC)?DM大鼠于第11周随机分为DM组7只和Resveratrol(DR)组6只,DR组给予Resveratrol 10 mg/(kg·d)灌胃,共4周?第14周收集3组大鼠24 h尿测尿微量白蛋白?处死大鼠,心脏取血测血肌酐?取肾组织,制石蜡切片做HE染色,免疫组化观察肾皮质4E-BP1磷酸化蛋白表达量的变化?Western blot检测肾皮质S6磷酸化蛋白表达的改变?结果:与NC组相比,DR和DM组大鼠血糖?24 h尿微量白蛋白和血肌酐明显升高,而体重明显降低(P均 < 0.01),而用Resveratrol干预后DR组大鼠血糖?24 h尿微量白蛋白及血肌酐比DM组明显好转(P < 0.05)?肾脏HE染色结果显示,DM组大鼠肾小球系膜基质中度增生,系膜细胞增生,系膜区明显扩大,肾小球体积增大?DR组肾小球系膜细胞和基质增生及肾小球系膜区扩张较DM组明显减轻?肾皮质免疫组化结果显示,4E-BP1磷酸化蛋白在DM组表达呈强阳性,在DR组表达呈弱阳性?DM和DR组大鼠血管组织中S6磷酸化蛋白的表达明显高于NC组(P < 0.01),而DR组明显低于DM组(P < 0.01)?结论:DM大鼠早期存在肾脏肥大和mTOR信号通路下游的4E-BP1和S6磷酸化蛋白表达增高?Resveratrol可能通过抑制4E-BP1和S6的磷酸化来减轻DM大鼠早期肾脏肥大,延缓糖尿病肾病的发展?

Effects of Resveratrol on the expressions of phosphorylation of 4E-BP1 and S6 protein in the renal cortex of diabetic rats

Objective:To investigate the effects of Resveratrol on the renal hypertrophy in early diabetic rats and the possible mechanism. Methods:A diabetic state was induced in 13 Spargue-Dawley rats by a single intraperitoneal injection of streptozotocin and then raised for 10 weeks. Six normal rats served as control (NC group). Diabetic rats were randomly divided into diabetic group (DM,n=7) and Resveratrol group (DR,n=6). Rats in DR group had been treated with Resveratrol 10 mg/(kg·d) intragastricly for 4 weeks. At the end of the experiments,the blood glucose (BG),body weight (BW),24 h urinary albumin excretion,serum creatinine of three groups were measuerd. Renal cortex was stained with hematoxylin and eosin. The expression of phosphorylation of 4E-BP1 protein was examined by immunohistochemistry. The expression of phosphorylation of S6 protein in the renal cortex was determined by Western blot. Results:The BW of rats in DM and DR groups decreased significantly,and the BG in DM and DR groups increased significantly compared with that in NC group (P < 0.01),and the BG of diabetic rats treated with Resveratrol improved compared with that in DM group (P < 0.05). Compared with normal rats,24 h urinary albumin excretion and serum creatinine significantly elevated in the DM and DR group (P < 0.01). 24 h urinary albumin excretion in DR group decreased significantly compared with that in DM group (P < 0.05). Resveratrol treatment attenuated glomerula mesangial cells hyperplasia,and reduced glomerula mesangial field enlargement and glomerula volume. The expressions of phosphorylation of 4E-BP1 and S6 protein in DM and DR groups were much higher than those in NC group (P < 0.01),but they were comparatively much lower in the DR group than those in DM group (P < 0.01). Conclusion:Resveratrol treatment can prevent the renal enlargement in early diabetic rats and thus halt the early step of the development of diabetic nephropathy. The mechanism is that Resveratrol may inhibit the phosphorylation of mTOR signal pathway downstream protein 4E-BP1 and S6.