[1]彭芬芬,李红瑜,尹柏辉,等.替米沙坦抑制单侧输尿管梗阻小鼠肾脏Mtdh表达而减轻肾脏纤维化[J].南方医科大学学报,2019,(02):156.[doi:10.12122/j.issn.1673-4254.2019.02.05]
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替米沙坦抑制单侧输尿管梗阻小鼠肾脏Mtdh表达而减轻肾脏纤维化()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2019年02期
页码:
156
栏目:
出版日期:
2019-02-28

文章信息/Info

Title:
Effect of telmisartan on expression of metadherin in the kidney of mice with unilateral ureter obstruction
作者:
彭芬芬李红瑜尹柏辉王育娴陈毅华许兆忠罗丛伟龙海波
关键词:
替米沙坦metadhein肾脏纤维化
Keywords:
telmisartan metadherin renal fibrosis
DOI:
10.12122/j.issn.1673-4254.2019.02.05
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(FN1)、α平滑肌蛋白(α-SMA)、胶原蛋白Ⅰ(ColⅠ)、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,FN1、α-SMA、Col Ⅰ和Mtdh表达显著升高(P<0.05),钙连蛋白表达显著下降(P<0.05); 替米沙坦干预后,肾脏纤维化病理减轻,FN1、α-SMA、Col Ⅰ及Mtdh表达显著下降(P<0.05),钙连蛋白表达回升(P<0.05)。采 用si-Mtdh下调肾小管上皮细胞Mtdh后,FN1、α-SMA、Col Ⅰ表达均显著下降(P<0.05),钙连蛋白表达回升(P<0.01)。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。
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 kidney of the mice. In the in vitro experiment, cultured mouse renal tubular epithelial cells (mTECs) were stimulated with transforming growth factor-β1 (TGF-β1) and transfected with a siRNA targeting metadherin, and the changes in the expressions of extracellular matrix proteins and metadherin were detected using Western blotting. Results The expressions of extracellular matrix proteins and metadherin increased significantly in the kidney of mice with UUO (P<0.05). Intervention with telmisartan significantly lowered the expressions of extracellular matrix proteins and metadherin and alleviated the pathology of renal fibrosis in mice with UUO (P<0.05). In cultured mTECs, siRNA-mediated knockdown of metadherin obviously reversed TGF-β1-induced increase in the expressions of extracellular matrix proteins and metadherin. Conclusion Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice.
更新日期/Last Update: 1900-01-01