目的 研究黄芪甲苷对高糖环境下足细胞线粒体分裂的影响及其保护作用.方法 体外培养小鼠肾小球足细胞,将细胞随机分为5组:对照组、模型组和低、中、高3个浓度实验组.对照组细胞以5.5 mmol·L-1低糖处理,模型组用30 mmol·L-1高糖处理,实验组用低、中、高3个浓度(20,40,80 μmol·L-1)黄芪甲苷预处理24 h后,再用30 mmol·L-1高糖处理.以流式细胞仪检测各组的足细胞凋亡率和线粒体膜电位;以蛋白免疫印迹实验测定足细胞沉默信息调节因子2相关酶1(Sirt1)/p53/线粒体动力相关蛋白(Drp1)信号通路表达情况.结果 对照组、模型组和低、中、高3个浓度实验组的足细胞凋亡率分别为(9.24±0.86)％,(43.15±0.51)％,(36.68±1.05)％,(25.55±0.71)％和(14.49±1.17)％;这5组的足细胞线粒体膜电位分别为5.01％,14.07％,8.70％,7.98％和7.35％;模型组与对照组相比或者低、中、高3个浓度实验组与模型组相比,差异均有统计学意义(均P<0.05).这5组的Sirt1蛋白表达量分别为0.97±0.01,0.45±0.03,0.55±0.02,0.64±0.02和0.95±0.02;这5组的p53蛋白表达量分别为0.21±0.02,0.40±0.02,0.34±0.01,0.26±0.02和0.22±0.01;这5组的Drp1蛋白表达量分为0.29±0.04,0.39±0.01,0.31±0.03,0.26±0.06和0.20±0.02;模型组与对照组相比或者高剂量实验组与模型组相比,差异均有统计学意义(均P<0.01).结论 黄芪甲苷改善高糖诱导足细胞线粒体异常分裂减少足细胞凋亡,这种保护机制可能部分与调控Sirt1/p53/Drp1信号通路有关.“,”Objective To investigate the effects and protection of Astragaloside Ⅳ on mitochondrial fission of mouse podocytes induced by high glucose. Methods The podocytes were cultured in vitro. Podocyte were divided into 5 groups: control group,model group and three concentration experimental groups. Podocyte in the control group was treated with 5. 5 mmol· L-1 glucose. Model group was treated with 30 mmol · L-1 glucose, three concentration experimental groups was pretreated with 20,40,80 μmol·L-1 Astragaloside Ⅳ for 24 h and then treated with 30 mmol·L-1 glucose. Apoptosis and the changes of mitochondrial membrane potential were detected by flow cytometry. Western blotting was used to detect the protein expression level of silent mating type information regulation 2 homolog-1 (Sirt1) ,p53,dynamin-related protein 1(Drp1). Results The podocytes apoptosis rates in control group,model group and low,middle,high concentration experimental groups were (9. 24 ± 0. 86) ％,(43. 15 ± 0. 51) ％,(36. 68 ± 1. 05) ％,(25. 55 ± 0. 71) ％ and (14. 49 ± 1. 17) ％; Mitochondrial transmembrane potential in the five groups were 5. 01％,14. 07％,8. 70％,7. 98％ and 7. 35％; comparison between model group and control group, the difference was significant(P < 0. 05); comparison between three concentration experimental groups and model group, the difference was significant(all P < 0. 05). The protein expression of Sirt1 in the five groups were 0. 97 ± 0. 01,0. 45 ± 0. 03,0. 55 ± 0. 02,0. 64 ± 0. 02 and 0. 95 ± 0. 02; the protein expression of p53 in the five groups were 0. 21 ± 0. 02,0. 40 ± 0. 02,0. 34 ± 0. 01,0. 26 ± 0. 02 and 0. 22 ± 0. 01; the protein expression of Drp1 in the five groups were 0. 29 ± 0. 04,0. 39 ± 0. 01,0. 31 ± 0. 03,0. 26 ± 0. 06 and 0. 20 ± 0. 02. Comparison between model group and control group, the difference of the factors were significant(P < 0. 01); comparison between high concentration experimental group and model group, the difference of the factors were significant (all P < 0. 01) . Conclusion The Astragaloside Ⅳ exerted a protective effect on podocytes injuried by high glucose,which may be related to activation of the Sirt1/p53/Drp1 signaling pathway,and subsequent attenuation of mitochondrial fission.