小檗碱调节PI3K/AKT/FOXO1/Bim信号通路改善高糖诱导的足细胞损伤  

Berberine regulates PI3K/AKT/FOXO1/Bim signaling pathway to improve high glucose-induced podocyte injury

作　　者：刘青 汪佳佳 胡亚琴 唐丽琴[1,2] 魏伟 LIU Qing;WANG Jia-jia;HU Ya-qin;TANG Li-qin;WEI Wei(Institute of Clinical Pharmacology,Anhui Medical University,Key Lab of Anti-inflammatory and Immune Medicine,Ministry of Education,Anhui Collaborative Innovation Center of Anhui-inflammatory and Immune Medicine,Hefei 230032,China;Dept of Pharmacy,Anhui Provincial Hospital,the First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药物教育部重点实验室,抗炎免疫药物安徽省协同创新中心,安徽合肥230032 [2]中国科学技术大学附属第一医院(安徽省立医院)药剂科,安徽合肥230001

出　　处：《中国药理学通报》2020年第3期329-334,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81773955);安徽省中医药科研课题(No 2016zy08);安徽省自然科学基金资助项目(No 1708085QH207)。

摘　　要：目的探讨小檗碱通过调节PI3K/AKT/FOXO1/Bim信号通路改善高糖诱导的足细胞损伤。方法用指数生长期的足细胞进行实验,实验分为正常对照组、高糖模型组、小檗碱作用组:浓度分别为30、60、90μmol·L^-1。CCK-8法检测细胞的存活率;Annexin V FITC/PI双色标记检测细胞的凋亡率;Transwell小室法考察细胞的迁移能力;Western blot法分析细胞上PI3K、p-AKT、p-FOXO1、Bim和足细胞标志蛋白nephrin、WT-1的表达情况。结果CCK-8检测结果显示,不同浓度的小檗碱对足细胞增殖能力的促进程度不同;An-nexin V FITC/PI双色标记细胞凋亡结果显示,小檗碱对高糖诱导的足细胞凋亡具有抑制作用;Transwell小室实验结果显示,小檗碱对高糖诱导的足细胞迁移具有抑制作用;Western blot的结果得出,小檗碱能明显升高nephrin、WT-1蛋白的表达,降低PI3K、p-AKT、Bim蛋白的表达,明显升高p-FOXO1蛋白的表达。结论小檗碱能缓解高糖诱导足细胞的损伤,其可能的机制与保护足细胞PI3K/AKT/FOXO1/Bim的信号通路有关。Aim To investigate the effect of berberine on high glucose-induced podocyte injury by regulating PI3K/AKT/FOXO1/Bim signaling pathway.Methods Experiments with glomerular podocytes in exponen-tial growth phase,the experiment was divided into five groups,namely,normal control group,high glucose model group and berberine treatment group,with con-centrations of 30,60,90μmol·L-1,respectively.The survival rate of cells was detected by CCK-8 method;the apoptosis rate of cells was detected by Annexin V FITC/PI two-color labeling;the migration ability of each group was examined by Transwell chamber meth-od;the expression of PI3K,p-AKT,p-FOXO1 and podocyte marker proteins nephrin and WT-1 were ana-lyzed by Western blot.Results The results of CCK-8 showed that different concentrations of berberine promoted the proliferation of podocytes induced by high glucose.The results of Annexin V FITC/PI two-color labeling apoptosis assay showed that berberine had an inhibitory effect on high glucose-induced podocyte ap-optosis.Transwell chamber test showed that berberine had an inhibitory effect on podocyte migration induced by high glucose.Western blot showed that berberine could significantly increase nephrin and WT-1 protein,significantly reduce the expression of PI3K,p-AKT,Bim protein,and increase p-FOXO1 protein expres-sion.Conclusions Berberine can alleviate the dam-age induced by high glucose in podocytes,and its pos-sible mechanism is related to protecting PI3K/AKT/FOXO1/Bim signaling pathway.

关 键 词：小檗碱 糖尿病肾病 足细胞 FOXO1 BIM 信号通路 

分 类 号：R-332[医药卫生] R284.1