替米沙坦抑制单侧输尿管梗阻小鼠肾脏Mtdh表达而减轻肾脏.PDFVIP

·156 · doi 10.12122/j.issn. 1673-4254.2019.09.05 J South Med Univ, 2019, 39(2): 156-161 替米沙坦抑制单侧输尿管梗阻小鼠肾脏替米沙坦抑制单侧输尿管梗阻小鼠肾脏MtdhMtdh 表达而减轻肾脏表达而减轻肾脏 纤维纤维化化 彭芬芬，李红瑜，尹柏辉，王育娴，陈毅华，许兆忠，罗丛伟，龙海波 南方医科大学珠江医院肾内科，广东 广州 510282 摘要：目的研究原癌基因metadhein（Mtdh）在单侧输尿管梗阻肾脏的表达及替米沙坦对其表达和肾脏纤维化的影响。方法 采 用单侧输尿管结扎梗阻建立肾间质纤维化小鼠模型和小管上皮细胞间质转分化模型。18只雄性C57小鼠随机分为假手术组， 单侧输尿管结扎梗阻、单侧输尿管结扎并替米沙坦干预组。MASSON 染色观察肾脏病理改变；免疫组织化学和Western blot 检 测各组细胞外基质蛋白纤连蛋白（FN 1）、α平滑肌蛋白（α-SMA ）、胶原蛋白Ⅰ（Col Ⅰ）、钙连蛋白和Mtdh 的表达情况；体外细胞 实验采用TGF-β1预刺激小鼠肾小管上皮细胞，并同时利用siRNA 干涉下调Mtdh ，Western blot 检测上述蛋白表达变化。结果 模型组肾脏纤维化显著高于假手术组，FN 1、α-SMA、Col Ⅰ和Mtdh 表达显著升高（P0.05），钙连蛋白表达显著下降（P0.05）； 替米沙坦干预后，肾脏纤维化病理减轻，FN 1、α-SMA、Col Ⅰ及Mtdh 表达显著下降（P0.05），钙连蛋白表达回升（P0.05）。采 用si-Mtdh下调肾小管上皮细胞Mtdh 后，FN 1、α-SMA、Col Ⅰ表达均显著下降（P0.05），钙连蛋白表达回升（P0.01）。结论 替 米沙坦可抑制细胞基质蛋白生成，抑制Mtdh 的表达，减轻小鼠肾脏纤维化。 关键词：替米沙坦；metadhein ；肾脏纤维化 Effect of telmisartan on expression of metadherin in the kidney of mice with unilateral ureter obstruction PENG Fenfen, LI Hongyu, YIN Bohui, WANG Yuxian, CHEN Yihua, XU Zhaozhong, LUO Chongwei, LONG Haibo Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China Abstract: Objective To explore the effect of telmisartan on the expression of metadherin in the kidney of mice with unilateral ureter obstruction. Methods Eighteen male C57 mice were randomized into sham-operated group, model group and telmisartan treatment group. In the latter two groups, renal interstitial fibrosis as the result of unilateral ureter obstruction (UUO) was induced by unilateral ureteral ligation with or without telmisartan intervention. Renal pathological changes of the mice were assessed using Masson staining, and immunohistochemistry and Western blotting were used to detect the expression of extracellular matrix proteins and metadherin in the ki