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

Nintedanib suppresses overexpression of extracellular matrix induced by angiotensin Ⅱ in renal fibroblasts

目的探讨尼达尼布(Nintedanib)对抗血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)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 AngⅡ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AngⅡ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AngⅡ诱导的PI3K/Akt信号通路的激活。Nintedanib还可以抑制AngⅡ引起的ROS水平升高。结论 Nintedanib可以抑制AngⅡ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。

Objective To investigate the effect of nintedanib on extracellular matrix production induced by angiotensin I[ （ Ang 11 ） 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. Results Ang Ⅱ induced the phosphorylation of PI3 K./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 AngⅡ. 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.