黄芪甲苷抑制高糖诱导的足细胞凋亡作用及机制

Astragaloside IV Inhibited High Glucose-Induced Podocyte Apoptosis and Its Mechanism

目的:探讨黄芪甲苷(AS-IV)对高糖诱导的足细胞凋亡的作用及其机制。方法:条件性永生的小鼠足细胞分为正常糖组(NG)、高糖组(HG)、甘露醇高渗对照组(MA)及HG+不同剂量(10、50、100μg/mL)黄芪甲苷干预组(AS-IV)。流式细胞仪及Hoechst染色检测细胞凋亡;荧光探针CM-H2-DCF-DA标记细胞检测活性氧(ROS)水平;Western印迹检测足细胞p38-MAPK活性。结果:高糖促进足细胞ROS的产生并引起足细胞凋亡,AS-IV明显抑制高糖诱导的ROS的产生及足细胞凋亡,且呈剂量依赖关系。此外,高糖激活p38-MAPK信号通路,AS-IV呈剂量依赖性抑制p38-MAPK活性。结论:AS-IV能减少高糖所致的足细胞凋亡,其机制可能与AS-IV抗氧化及抑制p38-MAPK活化密切相关。

Objective： To study the effects of Astragaloside IV（AS-IV） on glucose-induced apoptosis of podocytes and explore its possible mechanism. Methods： Conditionally immortalized mouse podocytes were divided into nomal glucose group （NG） , high glucose group （HG）, mannitol group （MA） and HG with 10, 50 and 100 μg/mL of AS-IV for 24h.Flow cytometry and Hoechst staning were used for the quantification of apoptotic podocytes. Reactive oxygen species （ROS） generation was measured with the fluoroprobe carboxymethyl-H2-dichlorofluorescein diacetate. The activation of p38-MAPK was determined by Western blot. Results： HG induced ROS generation and apoptosis of podocytes. AS-IV inhibited HG-induced ROS generation and apoptosis of podocytes in a dose-dependent manner. Moreover, HG caused p38-MAPK activation in podocytes, while AS-IV dose-dependently inhibited p38-MAPK activation.Conclusion： Astragaloside prevented high glucose-induced podocyte apoptosis and this effect may be involved in inhibition of ROS and p38-MAPK.