基于铁死亡探讨益母草碱对高糖诱导的肾足细胞损伤的保护作用  

The protective effect of leonurine on high glucose-induced podocyte injury based on ferroptosis

作　　者：王晶 闫晓辉[1] 王晓明[1] 朱燕亭 金刚[1] 丁通[1] 吴冰 WANG Jing;YAN Xiaohui;WANG Xiaoming;ZHU Yanting;JIN Gang;DING Tong;WU Bing(Nephrotic Hemodialysis Center,Shaanxi Provincial People's Hospital,Xi'an 710068,China)

机构地区：[1]陕西省人民医院肾病血透中心,陕西西安710068

出　　处：《西部医学》2025年第2期162-167,共6页Medical Journal of West China

基　　金：陕西省自然科学基础研究计划项目(2023-JC-YB-743)。

摘　　要：目的 探讨益母草碱是否通过调控铁死亡抑制高糖诱导的肾足细胞损伤。方法 将小鼠肾足细胞分为正常对照组、高糖组、高糖+益母草碱组、高糖+益母草碱+Erastin(铁死亡激活剂)组。采用细胞计数试剂盒-8(CCK-8)方法检测足细胞存活率。采用乳酸脱氢酶(LDH)试剂盒检测足细胞死亡。采用脂质过氧化探针和脂质过氧化丙二醛(MDA)试剂盒检测脂质过氧化反应。采用谷胱甘肽(GSH)测定试剂盒检测GSH含量。采用铁离子比色法测试盒检测铁离子浓度。采用Western blot检测铁死亡标志物GPX4、TFR1和ACSL4的蛋白表达水平。结果 与正常对照组比较,高糖组足细胞损伤显著增加,脂质过氧化水平显著提高,GSH含量显著减少,铁离子浓度显著升高,GPX4蛋白水平显著下调,TFR1和ACSL4的蛋白水平显著上调(均P<0.01)。与高糖组比较,高糖+益母草碱组足细胞损伤和脂质过氧化水平显著下降,GSH含量显著增加,铁离子浓度显著降低,GPX4蛋白水平显著上调,TFR1和ACSL4的蛋白水平显著下调(均P<0.01)。与高糖+益母草碱组比较,高糖+益母草碱+Erastin组足细胞损伤增加,脂质氧化水平显著升高,GSH含量显著减少,铁离子浓度显著升高,GPX4蛋白水平表达水平显著减少,TFR1和ACSL4蛋白表达显著增加(均P<0.05)。结论 益母草碱通过抑制铁死亡减轻高糖诱导的肾足细胞损伤。Objective To investigate the effect of leonurine on podocyte injury induced by high glucose through the regulation of ferroptosis.Methods The mouse podocytes were divided into four groups:the normal control group,the high glucose group,the high glucose + leonurine group,and the high glucose + leonurine + Erastin(ferroptosis inducer) group.The survival rate of the podocytes was assessed using the cell counting kit-8(CCK-8) assay.The death of the podocytes was determined using the lactate dehydrogenase(LDH) cytotoxicity assay kit.Lipid peroxidation was measured using a lipid peroxidation probe and a malondialdehyde(MDA) assay kit.The content of glutathione(GSH) was measured using a GSH assay kit.The concentration of iron was detected using an iron colorimetric assay kit.The protein levels of the ferroptosis markers GPX4,TFR1,and ACSL4 were measured using Western blot analysis.Results In comparison to the normal control group,the high glucose group exhibited significant podocyte injury,elevated lipid peroxidation,decreased GSH content,increased iron concentration,downregulated GPX4 protein level,and increased TFR1 and ACSL4 protein levels(P<0.01).In comparison to the high glucose group,the high glucose + leonurine group showed a significant decrease in podocyte injury,a reduction in lipid peroxidation,an increase in GSH content,a decrease in iron concentration,an upregulation of GPX4 protein levels,and a decrease in TFR1 and ACSL4 protein levels(P<0.01).In comparison to the high glucose+leonurine group,the high glucose + leonurine + Erastin group showed a significant increase in podocyte injury,lipid peroxidation,and ferroptosis(P<0.05).Conclusion Leonurine demonstrates ameliorative effects on podocyte injury induced by high glucose through the inhibition of ferroptosis.

关 键 词：足细胞 高糖 铁死亡 益母草碱 

分 类 号：R587.2[医药卫生—内分泌]