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  • 王艳道,余晨.Nintedanib对Ang Ⅱ诱导肾脏成纤维细胞产生细胞外基质的拮抗作用[J].同济大学学报(医学版),2015,36(4):13-18.    [点击复制]
  • WANG Yan-dao,YU Chen.Nintedanib suppresses overexpression of extracellular matrix induced by angiotensin Ⅱ in renal fibroblasts[J].同济大学学报(医学版),2015,36(4):13-18.   [点击复制]
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Nintedanib对Ang Ⅱ诱导肾脏成纤维细胞产生细胞外基质的拮抗作用
王艳道,余晨
0
(同济大学附属同济医院肾内科,上海 200065)
摘要:
目的探讨尼达尼布(Nintedanib)对抗血管紧张素Ⅱ(angiotensin Ⅱ, Ang Ⅱ)诱导的肾脏成纤维细胞产生细胞外基质的作用及其机制。方法 Ang Ⅱ处理大鼠肾脏成纤维细胞(NRK-49F),Western 印迹法检测相关分子的蛋白表达量,DHE荧光探针法检测活性氧簇(ROS)的水平。结果 肾脏成纤维细胞中Ang Ⅱ通过诱导PI3K/Akt 信号通路的激活,引起纤维连接蛋白和胶原蛋白Ⅰ的积聚。Nintedanib能抑制Ang Ⅱ诱导的PI3K/Akt信号通路的激活。Nintedanib还可以抑制Ang Ⅱ引起的ROS水平升高。结论 Nintedanib可以抑制Ang Ⅱ诱导的ECM成分升高,其作用机制与其抑制PI3K/Akt激活并抑制ROS产生有关。
关键词:  尼达尼布  PI3K/Akt  活性氧簇  血管紧张素Ⅱ  肾脏纤维化  大鼠
DOI:10.16118/j.1008-0392.2015.04.003
投稿时间:2015-02-26
基金项目:国家自然科学基金(81370790)
Nintedanib suppresses overexpression of extracellular matrix induced by angiotensin Ⅱ in renal fibroblasts
WANG Yan-dao,YU Chen
(Dept. of Nephrology, Tongji Hospital, Tongji University, Shanghai 200065, China)
Abstract:
Objective To investigate the effect of nintedanib on extracellular matrix production induced by angiotensin Ⅱ(Ang Ⅱ) in renal fibroblasts and related mechanism. Methods Renal fibroblast cells were treated with Ang Ⅱ. Expression of fibronectin, collagen Ⅰ levels was determined by Western blotting, and the ROS level was detected by DHE fluorescent probe. ResultsAng Ⅱ induced the phosphorylation of PI3K/Akt signalling, with the accumulation of fibronectin and collagen Ⅰ in renal fibroblast cells. Nintedanib blocked the phosphorylation of Akt and attenuated the increase of fibronectin and collagen Ⅰ induced by Ang Ⅱ. Nintedanib also inhibited Ang Ⅱ induced ROS generation. Conclusion Nintedanib can attenuate the accumulation of ECM proteins induced by Ang Ⅱ, which may be associated with the suppression effect on PI3K/Akt signalling activation and subsequent ROS overproduction.
Key words:  Nintedanib  PI3K/Akt  reactive oxygen species  angiotensin Ⅱ  renal fibrosis  rat

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