中文摘要：

目的探究非肽类Ang（1-7）受体激动剂AVE0991对链脲佐菌素（STZ）诱导的大鼠糖尿病肾病（DN）的保护作用。方法 30只Wistar大鼠随机分为3组：正常对照组（NC组）、糖尿病肾病组（DN组）、AVE0991处理组（AVE组）,每组10只。DN组与AVE组腹腔注射STZ（65 mg/kg）,STZ注射8周后,给予AVE组AVE0991灌胃处理,NC组及DN组取等量生理盐水灌胃,连续灌胃4周。12周末收集标本,检测各项生理生化指标;高碘酸-希夫（PAS）及免疫组化观察各组肾脏病理变化;实时荧光定量PCR及酶联免疫吸附实验（ELISA）法分别检测白介素1β（IL-1β）、白介素6（IL-6）和肿瘤坏死因子α（TNF-α）的mRNA及蛋白水平变化。结果与NC组相比,DN组与AVE组大鼠血肌酐、24 h尿蛋白定量、肾质量体质量比明显升高,肾小球硬化指数、胶原Ⅰ（CollagenⅠ）表达量、炎症因子IL-1β、IL-6、TNF-αmRNA及蛋白水平明显上升。AVE组与DN组相比,大鼠血肌酐、24 h尿蛋白定量、肾小球硬化指数、CollagenⅠ表达量及肾组织炎症因子IL-1β、IL-6、TNF-αmRNA及蛋白表达均明显降低（P〈0.01）。结论 AVE0991可以降低大鼠DN的纤维化及炎症水平。

英文摘要：

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-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-6and 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.