六味地黄汤下调NF-κB/NLRP3信号通路抑制HK-2细胞焦亡延缓肾纤维化  

Liuwei Dihuang Decoction(六味地黄汤)Inhibits Pyroptosis of HK-2 Cells and Delays Renal Fibrosis by Downregulating NF-κB/NLRP3 Signaling Pathway

作　　者：马秀英 黄娜 杨成[1] 汪涵俪 裴刚[1] 孟斌(指导)[1] 唐群[1] MA Xiuying;HUANG Na;YANG Cheng;WANG Hanli;PEI Gang;MENG Bin;TANG Qun(Hunan University Of Chinese Medicine,Changsha 410208)

机构地区：[1]湖南中医药大学,长沙410208

出　　处：《中药药理与临床》2025年第1期28-32,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：湖南省自然科学基金项目(编号:2021JJ30506);湖南省教育厅重点项目(编号:21A0242);湖南中医药大学科研项目(编号:Z2023XJYB04);湖南中医药大学重点学科—基础医学;湖南省大学生创新创业训练计划项目(编号:S202210541144)。

摘　　要：目的:探讨六味地黄汤对转化生长因子β1(TGF-β1)诱导肾小管上皮细胞(HK-2)的肾纤维化模型的治疗效果及作用机制。方法:体外培养HK-2细胞并随机分为:正常对照血清组、模型对照组、六味地黄汤含药血清5%、10%、20%组和MCC9501μmol/L组。除正常对照血清组外,其余各组细胞给予10 ng/m L TGF-β1诱导肾纤维化,并予以相应药物干预。给药24 h后收集细胞,以RT-q PCR法、Western blot法、免疫荧光法测定NF-κB/NLRP3信号通路及焦亡、肾纤维化相关指标表达。结果:与正常对照组相比,模型对照组HK-2细胞Nfkb、Nlrp3、Caspase1、Il18 mRNA表达上调(P<0.05),NF-κB、Caspase-1、IL-1β、IL-18、Vimentin蛋白表达上调(P<0.05),E-cadherin蛋白表达下调(P<0.05);与模型对照组相比,六味地黄汤含药血清10%、20%组和MCC9501μmol/L组HK-2细胞Nfkb、Nlrp3、Caspase1、Il18 mRNA表达下调(P<0.05),NF-κB、Caspase-1、IL-1β、IL-18、Vimentin蛋白表达下调(P<0.05),Ecadherin蛋白表达上调(P<0.05)。结论:六味地黄汤能抑制肾小管上皮细胞焦亡,延缓肾纤维化,其机制可能与下调NF-κB/NLRP3信号通路相关。Objective:To investigate the therapeutic effect and mechanism of Liuwei Dihuang Decoction(六味地黄汤)on renal fibrosis in a model of transforming growth factorβ1(TGF-β1)-induced renal tubular epithelial cells(HK-2).Methods:HK-2 cells were cultured in vitro and randomly divided into the following groups:normal control group,model control group,Liuwei Dihuang Decoction-medicated serum 5%,10%,and20%groups,and MCC9501μmol/L group.Except for the normal control group,the other groups were induced with 10 ng/m L TGF-β1 to induce a renal fibrosis model and were intervened with corresponding drugs.After 24 hours of administration,cells were collected and the expression of NF-κB/NLRP3 signaling pathway and related indicators of pyroptosis and renal fibrosis were measured using RT-q PCR,Western blot,and immunofluorescence methods.Results:Compared with the normal control group,the model control group had upregulated expression of NF-κB,Caspase-1,IL-1β,IL-18,and Vimentin proteins in HK-2 cells(P<0.05),downregulated expression of E-cadherin protein(P<0.05),and upregulated mRNA expression levels of Nf-κb,Nlrp3,Caspase-1,and Il-18(P<0.05).Compared with the model control group,the Liuwei Dihuang Decoction-medicated serum 10%and 20%groups and the MCC9501μmol/L group had downregulated expression of NF-κB,Caspase-1,IL-1β,IL-18,and Vimentin proteins in HK-2 cells(P<0.05),upregulated expression of E-cadherin protein(P<0.05),and downregulated mRNA expression levels of Nf-κb,Nlrp3,Caspase-1,and Il-18(P<0.05).Conclusion:Liuwei Dihuang Decoction can inhibit pyroptosis in renal tubular epithelial cells and delay renal fibrosis,potentially through the downregulation of the NF-κB/NLRP3 signaling pathway.

关 键 词：六味地黄汤 细胞焦亡 肾纤维化 HK-2细胞 核因子κB/核苷酸结合寡聚化结构域样受体蛋白3信号通路 

分 类 号：R285[医药卫生—中药学]