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。 Objective: To investigate the effect of Resveratrol on early renal hypertrophy in diabetic rats and its possible mechanism. Methods: Thirteen male SD rats were induced with streptozotocin (DM) and 6 normal SD rats were used as control (NC). The DM rats were randomly divided into DM group (7 rats) and Resveratrol group (6 rats) in the 11th week. DR group was administrated with Resveratrol 10 mg / (kg.d) for 4 weeks. At the 14th week, urine microalbuminuria was measured in 24 hours in 3 groups of rats. The rats were sacrificed and the blood was taken from the heart to measure serum creatinine. The kidney tissue and paraffin sections were made into HE staining. The expression of 4E-BP1 phosphorylation protein in renal cortex was observed by immunohistochemistry. Western blot detection of renal cortex S6 phosphorylation protein expression changes. Results: Compared with NC group, the blood glucose, 24 h urinary albumin and serum creatinine were significantly increased in DR and DM rats and the body weight was significantly decreased (P <0.01), while the levels of blood glucose , 24h urinary albumin and serum creatinine than the DM group was significantly improved (P <0.05). The results of kidney HE staining showed that the glomerular mesangial matrix of DM rats proliferated moderately, the mesangial cells proliferated, the mesangial area enlarged obviously, and the glomerular volume increased. Compared with DM group, the number of glomerular mesangial cells, matrix hyperplasia and mesangial expansion in DR group were significantly decreased. Renal cortical immunohistochemistry results showed that 4E-BP1 phosphorylation protein was strongly positive in DM group, and weakly positive in DR group. The expression of S6 phosphorylation protein in DM and DR groups was significantly higher than that in NC group (P <0.01), while it was significantly lower in DR group than that in DM group (P <0.01). CONCLUSION: Early renal hypertrophy in DM rats and the expression of phosphorylated 4E-BP1 and S6 phosphorylation in the downstream of mTOR signaling pathway are increased. Resveratrol may reduce the early renal hypertrophy and delay the development of diabetic nephropathy by inhibiting the phosphorylation of 4E-BP1 and S6.