北京中医药大学学报2024，Vol.47Issue(10)：1408-1415,8.DOI:10.3969/j.issn.1006-2157.2024.10.011
黄芪皂苷Ⅰ通过抑制足细胞焦亡干预糖尿病肾脏疾病的机制研究
Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease
摘要
Abstract
Objective To investigate the mechanism of astragaloside Ⅰ,the active constituent of milkvetch root,in inhibiting podocyte injury and improving diabetic kidney disease.Methods According to the body weight,60 male db/db mice were randomly divided into the model group,astragaloside Ⅰ low-dose group(10 mg/kg),astragaloside Ⅰ medium-dose group(20 mg/kg),astragaloside Ⅰ high-dose group(40 mg/kg),and valsartan group(10mg/kg),with 12 mice per group.Twelve db/db littermate control db/m mice were used as the control group.The drug was administered by gavage for 8 weeks.Transmission electron microscope was used to observe the ultrastructure of the kidney;immunohistochemistry and Western blotting were used to detect the expression of nephrotic protein(nephrin),a marker of renal podocytes;enzyme-linked immunosorbent assay was used to detect the contents of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the serum of mice;Western blotting was used to detect the protein expressions of NOD-like receptor thermoprotein domain-related protein 3(NLRP3),cysteinyl aspartate specific proteinase 1(Caspase-1),and Gasdermin D(GSDMD)in kidney tissue.Results Compared with the control group,the glomeruli of the model group showed obvious podocyte loss and foot process fusion;the protein expression of nephrin was decreased(P＜0.05);the contents of IL-1 β and IL-18 in serum were increased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were increased(P＜0.05).Compared with the model group,the renal pathological damage in the astragaloside Ⅰ administration groups were alleviated;the protein expression of nephrin was increased(P＜0.05);the contents of IL-1β and IL-18 in serum were decreased(P＜0.05);the protein expressions of NLRP3,Cleaved-Caspase-1,and GSDMD-N were decreased(P＜0.05).Conclusion Astragaloside Ⅰ may play a role in intervening diabetic kidney disease by inhibiting pyroptosis and improving podocyte injury.关键词
黄芪/黄芪皂苷Ⅰ/糖尿病肾脏疾病/足细胞/细胞焦亡/小鼠Key words
milkvetch root/astragaloside Ⅰ/diabetic kidney disease/podocytes/pyroptosis/mice分类
医药卫生引用本文复制引用
段亚飞,谢治深,张效威,石贤聪,赵靓,吕明真,任心棋,古豫蕾,徐江雁,张振强,苗晋鑫..黄芪皂苷Ⅰ通过抑制足细胞焦亡干预糖尿病肾脏疾病的机制研究[J].北京中医药大学学报,2024,47(10):1408-1415,8.基金项目
国家重点研发计划项目(No.2020YFE0201800) （No.2020YFE0201800）
国家自然科学基金项目(No.82104471) （No.82104471）
河南省重点研发专项(No.221111520300) （No.221111520300）
河南省省级科技研发计划联合基金(No.232301420093) （No.232301420093）
河南省高校科技创新人才支持计划(No.24HASTIT072) （No.24HASTIT072）
国家中医药管理局国际合作司中医药国际合作专项(基地类项目)(No.0730-236132ZC0054/01-05) National Key R&D Program(No.2020YFE0201800) （基地类项目）
