文献类型：期刊文献

中文题名：淫羊藿苷联合地塞米松对阿霉素诱导足细胞损伤的保护作用

英文题名：Protective Effect of Icariin Combined with Dexamethasone against Adriamycin-induced Podocyte Injury

作者：白俊嫄[1];戴恩来[2];蒲晓薇[2];张云霞[3]

第一作者：白俊嫄

机构：[1]甘肃中医药大学附属医院,兰州730020;[2]甘肃中医药大学,兰州730020;[3]甘肃省中医院,兰州730050

第一机构：甘肃中医药大学第二附属医院

年份：2025

卷号：20

期号：9

起止页码：1506

中文期刊名：世界中医药

外文期刊名：World Chinese Medicine

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金项目(82160852)——基于TRPC6介导Ca^(2+)-CaM-CaN通路探讨淫羊藿苷对激素抵抗型肾病综合征大鼠足细胞功能保护的分子机制。

语种：中文

中文关键词：激素抵抗型肾病综合征;局灶节段性肾小球硬化;足细胞;细胞骨架;阿霉素足细胞损伤;淫羊藿苷;地塞米松;无翅型MMTV整合位点家族成员1/β-连环蛋白/瞬时受体电位阳离子通道6/钙调神经磷酸酶通路

外文关键词：Steroid-resistant nephrotic syndrome;Focal segmental glomerulosclerosis;Podocyte;Cytoskeleton;Adriamycin-induced podocyte injury;Icariin;Dexamethasone;Wnt/β-catenin/TRPC6/CaN pathway

摘要：目的:探讨淫羊藿苷联合地塞米松对阿霉素诱导足细胞损伤的保护作用,及对无翅型MMTV整合位点家族成员1(Wnt1)、β-连环蛋白(β-catenin)、瞬时受体电位阳离子通道6蛋白(TRPC6)、钙调蛋白(CAM)、钙调神经磷酸酶(CAN)、活化T细胞核因子(NFAT)、F-肌动蛋白(F-actin)及肌球蛋白重链9(MYH9)表达的影响。方法:采用阿霉素诱导大鼠肾足细胞建立足细胞损伤模型,分为空白组、模型组、地塞米松组、淫羊藿苷组、联合组。通过检测足细胞活力、凋亡率、细胞内钙离子浓度,观察足细胞骨架结构和损伤超微结构,分析Wnt/β-catenin/TRPC6/CaN通路相关转接分子表达规律。结果:与空白组比较,模型组足细胞存活率显著降低(P<0.01),总凋亡率显著升高(P<0.01),[Ca^(2+)]i浓度增强(P<0.01),足细胞骨架排列紊乱、重组且降解,足突广泛融合,足细胞Wnt、β-catenin、TRPC6、CaM、CaN以及NFAT基因和蛋白表达均显著升高(P<0.01),F-actin和MYH9表达均显著降低(P<0.01)。与模型组比较,联合组足细胞存活率升高(P<0.01),总凋亡率下降(P<0.01),[Ca^(2+)]i浓度显著降低(P<0.01),足细胞骨架紊乱好转,足细胞微观结构趋于正常,足细胞Wnt、β-catenin、TRPC6、CaM、CaN、NFAT基因和蛋白表达显著低于模型组(P<0.01),F-actin和MYH9表达显著高于模型组(P<0.01)。结论:淫羊藿苷联合地塞米松可能通过干预Wnt/β-catenin/TRPC6/CaN信号通路的过度激活而抑制钙离子内流,改善足细胞骨架蛋白结构、保护足细胞功能,进而发挥激素增敏作用。
Objective:To investigate the protective effect of icariin combined with dexamethasone against adriamycin-induced podocyte injury,and their influence on the expression of wingless-type MMTV integration site family member 1(Wnt1),β-catenin,transient receptor potential cation channel 6(TRPC6),calmodulin(CaM),calcineurin(CaN),activated T-cell nuclear factor(NFAT),F-actin,and myosin heavy chain 9(MYH9).Methods:A podocyte injury model was established by inducing rat renal podocytes with adriamycin.The cells were divided into blank,model,dexamethasone,icariin,and combination treatment groups.Podocyte viability,apoptosis rate,and intracellular calcium concentration([Ca^(2+)]i)were measured.Podocyte cytoskeletal structure and ultrastructural damage were observed,and the expression patterns of molecules related to the Wnt/β-catenin/TRPC6/CaN signaling pathway were analyzed.Results:Compared with the blank group,the model group showed significantly decreased podocyte viability(P<0.01),increased total apoptosis rate(P<0.01),and elevated[Ca^(2+)]i concentration(P<0.01).Podocyte cytoskeleton was disorganized,remodeled,and degraded,with extensive foot process fusion.Gene and protein expression levels of Wnt,β-catenin,TRPC6,CaM,CaN,and NFAT were significantly increased(P<0.01),while expression levels of F-actin and MYH9 were significantly decreased(P<0.01).Compared with the model group,the combination treatment group showed increased podocyte viability(P<0.01),decreased total apoptosis rate(P<0.01),and significantly reduced[Ca^(2+)]i concentration(P<0.01).Cytoskeletal disorganization improved,podocyte ultrastructure tended toward normal,and gene and protein expression levels of Wnt,β-catenin,TRPC6,CaM,CaN,and NFAT were significantly lower(P<0.01),whereas F-actin and MYH9 expression levels were significantly higher(P<0.01).Conclusion:Icariin combined with dexamethasone may exert hormone-sensitizing effects by inhibiting calcium influx through intervening in the overactivation of the Wnt/β-catenin/TRPC6/CaN signaling pathway,thereby improving podocyte cytoskeletal protein structure and protecting podocyte function.