Abstract: Objective To explore the protective effect of AVE0991, a non-peptide Ang(1-7)receptor agonist, on rat models of diabetic nephropathy. Methods A total of 30 male Wistar rats were randomly divided into 3 groups: normal control group(NC group, n=10), streptozotocin(STZ)induced diabetic nephropathy group(DN group, n=10)and AVE0991 treatment group(AVE group, n=10). After the DN group and AVE group received intraperitoneal injection of streptozotocin(STZ)65 mg/kg for 8 weeks, the AVE group received AVE0991 via gavage, and the DN and NC groups received normal saline of the same amount for 4 weeks continuously. Then the renal functional and bio-chemical parameters were measured. Renal pathological changes of each group were observed by Periodic Acid Schiff(PAS)staining and immunohistochemistry. The mRNA protein levels of IL-1β, IL-6, and TNF-α were determined by quanti- 山 东 大 学 学 报 (医 学 版)54卷10期 -陈志新,等.非肽类Ang(1-7)受体激动剂AVE0991对大鼠糖尿病肾病的保护作用 \=-fication real-time PCR. The concentrations of IL-1β, IL-6 and TNF-α protein levels were measured by ELISA. Results Compared with the NC group, the DN and AVE groups exhibited increased serum creatinine, 24 h-urine protein excretion, glomerulosclerositic index, expression of CollagenⅠas well as increased mRNA protein levels of IL-1β, IL-6 and TNF-α. Treatment of diabetic nephropathy with AVE0991 exhibited renal protective effect, as evidenced by a significant decrease in serum creatinine, 24 h-urine protein excretion, glomerulosclerositic index and downregulation of inflammatory factors(IL-1β, IL-6, TNF-α). Conclusion AVE0991 may have therapeutic potential in diabetic nephropathy by alleviating fibrosis and inflammation in kidney.

Key words: AVE0991, Ang(1-7)receptor agonist, Diabetes nephropathy, Rats, Wistar, Ang(1-7)