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山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (10): 29-33.doi: 10.6040/j.issn.1671-7554.0.2015.1184

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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

陈志新1,2,王颖3,曹新冉2, 黑乃豪2,李俊龙2,董波2,关广聚1   

  1. 1.山东大学肾脏病研究所 山东大学第二医院肾内科, 山东 济南 250033;2.山东大学附属省立医院心内科, 山东 济南 250021;3.德州市立医院老年科, 山东 德州 253000
  • 收稿日期:2015-11-27 出版日期:2016-10-10 发布日期:2016-10-10
  • 通讯作者: 关广聚. E-mail:guangj@sdu.edu.cn; 董波. E-mail:bodong@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(81170207,81570653);山东省医药卫生科技发展计划(2011HD004);济南市高校院所自主创新计划(200906011-1)

Evaluation of the protective effect of AVE0991 on streptozotocin-induced diabetic nephropathy rats

CHEN Zhixin1,2, WANG Ying3, CAO Xinran2, HEI Naihao2, LI Junlong2, DONG Bo2, GUAN Guangju1   

  1. 1. Nephrology Research Institute, Shandong University, Department of Nephrology, Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    2. Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    3. Department of Geriatrics, Municipal Hospital of Dezhou, Dezhou 253000, Shandong, China
  • Received:2015-11-27 Online:2016-10-10 Published:2016-10-10

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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-α mRNA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-α mRNA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。

关键词: 血管紧张素(1-7)受体激动剂, 糖尿病肾病, AVE0991, 血管紧张素1-7, Wistar, 大鼠

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)

中图分类号: 

  • R587.2
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