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

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国家科技期刊平台
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中文摘要：目的探讨黄芪活性成分黄芪皂苷Ⅰ抑制足细胞损伤、改善糖尿病肾脏疾病的作用机制。方法 60只雄性db/db小鼠按体质量随机分为模型组、黄芪皂苷Ⅰ低剂量组(10 mg/kg)、黄芪皂苷Ⅰ中剂量组(20 mg/kg)、黄芪皂苷Ⅰ高剂量组(40 mg/kg)及缬沙坦组(10 mg/kg)，每组12只;12只db/db同窝对照db/m小鼠作为对照组。灌胃给药8周。透射电子显微镜观察肾脏超微结构;免疫组织化学法、蛋白质印迹法检测肾脏足细胞标志物肾病蛋白(nephrin)的表达情况;酶联免疫吸附测定法检测小鼠血清白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)含量;蛋白质印迹法检测肾脏组织NOD样受体热蛋白结构域相关蛋白3(NLRP3)、胱天蛋白酶-1(Caspase-1)、消皮素D(GSDMD)蛋白表达。结果与对照组比较，模型组小鼠肾小球出现明显的足细胞丢失、足突融合等现象;肾脏nephrin蛋白表达下降(P＜0。05);血清IL-1β、IL-18含量升高(均P＜0。05);NLRP3、裂解型Caspase-1(Cleaved-Caspase-1)、GSDMD-N蛋白表达升高(均P＜0。05)。与模型组比较，黄芪皂苷Ⅰ给药组肾脏病理损伤得到缓解;Nephein蛋白表达升高(P＜0。05);血清IL-1β、IL-18含量下降(均 P＜0。05);NLRP3、Cleaved-Caspase-1、GSDMD-N 蛋白表达下降(均 P＜0。05)。结论黄芪皂苷Ⅰ可能通过抑制细胞焦亡、改善足细胞损伤发挥干预糖尿病肾脏疾病的作用。

外文标题：Study on the mechanism of astragaloside Ⅰ inhibiting podocyte pyroptosis in diabetic kidney disease

外文摘要：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.

外文关键词：

milkvetch rootastragaloside Ⅰdiabetic kidney diseasepodocytespyroptosismice

作者：

段亚飞、石贤聪、赵靓、吕明真、任心棋、古豫蕾、徐江雁、张振强、苗晋鑫、谢治深、张效威

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作者单位：

河南中医药大学中医药科学院郑州 450046

河南中医药大学豫药全产业链研发河南省协同创新中心

河南中医药大学中医学院

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

基金：

国家重点研发计划项目国家自然科学基金项目河南省重点研发专项河南省省级科技研发计划联合基金河南省高校科技创新人才支持计划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)

项目编号：

2020YFE02018008210447122111152030023230142009324HASTIT0720730-236132ZC0054/01-05

出版年：

2024

DOI：

10.3969/j.issn.1006-2157.2024.10.011

北京中医药大学学报

北京中医药大学

北京中医药大学学报

CSTPCD北大核心

影响因子：1.568

ISSN：1006-2157

年,卷(期)：2024.47(10)