解毒化瘀颗粒通过增强GPX4表达抑制急性肝衰竭小鼠模型中的肝细胞铁死亡  

Detoxification stasis granules inhibit hepatocellular ferrozozois in mouse models of acute liver failure by enhancing GPX4 expression

作　　者：刘美燕 林镛 黄小桃 卢昌林 刘志芳 梅梦如 陈炳东 曹音 毛德文[3,4] 龙富立[3,4] LIU Mei-yan;LIN Yong;HUANG Xiao-tao;LU Chang-lin;LIU Zhi-fang;MEI Meng-ru;CHEN Bing-dong;CAO Yin;MAO De-wen;LONG Fu-li(Graduate School of Guangxi University of Chinese Medicine,Nanning 530200,China;School of Traditional Chinese Medicine(Guangxi School of Traditional Chinese Medicine),Nanning,Guangxi,530023,China;First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning,Guangxi,530023,China;Guangxi Key Laboratory of Molecular Biology of Preventive Medicine of Traditional Chinese Medicine Nanjing 530023,China)

机构地区：[1]广西中医药大学研究生学院,广西南宁530200 [2]广西中医药大学附设中医学校(广西中医学校),广西南宁530023 [3]广西中医药大学第一附属医院,广西南宁530023 [4]广西中医药防治医学分子生物重点实验室,广西南宁530023

出　　处：《时珍国医国药》2024年第6期1306-1311,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(82260907,82274434);广西中医药适宜技术开发与推广项目(GZSY23-30);广西中医药大学国家青年岐黄学者培养项目;广西硕士研究生创新项目(YCSW2023397)。

摘　　要：目的探讨解毒化瘀颗粒(JDHY)治疗D-氨基半乳糖/脂多糖(D-GalN/LPS)诱导的ALF体外模型的潜在机制。方法采用不同浓度的D-GalN/LPS构建ALF肝损伤模型,并采用不同浓度的JDHY含药血清与ALF肝损模型进行共培养,明确JDHY的最佳浓度和共培养时间。随后,在体外分析了JDHY的可能分子机制。结果生化分析和细胞活力结果表明,JDHY能有效减轻ALF肝细胞损伤。铁离子浓度、MDA、Western Blot、ELISA检测表明JDHY可减少不稳定铁(Fe^(2+))的积累,减轻脂质过氧化,并增加了FTH1蛋白、降低TFR1蛋白表达、抑制铁死亡和炎症表达水平(TNF-α、IL-6);其机制可能与JDHY恢复了GSH/GPX4的代谢活性,增强了抗氧化反应,进而抑制了LOX/PTGS的通路进程有关。结论JDHY可能是通过引起ALF肝细胞的重编程促进了GSH/GPX4的抗氧化活性,从而抑制了肝细胞铁死亡。Objective To investigate the potential mechanism of JDHY in the treatment of D-aminogalactose/lipopolysaccharide(D-GalN/LPS)-induced ALF in vitro.Methods Different concentrations of D-GalN/LPS were used to construct the ALF liver injury model,and different concentrations of JDHY drug-containing serum were co-cultured with the ALF liver damage model,and the optimal concentration and co-culture time of JDHY were determined.Subsequently,the possible molecular mechanisms of JDHY were analyzed in vitro.Results Biochemical analysis and cell viability results showed that JDHY could effectively alleviate ALF hepatocyte injury.The results of iron ion concentration,MDA,Western blot and ELISA showed that JDHY could reduce the accumulation of unstable iron(Fe2+),alleviate lipid peroxidation,increase FTH1 protein,reduce TFR1 protein expression,and inhibit ferroptosis and inflammatory expression levels(TNF-α,IL-6).The mechanism may be related to the fact that JDHY restored the metabolic activity of GSH/GPX4 and enhanced the antioxidant response,thereby inhibiting the process of LOX/PTGS pathway.Conclusion JDHY may promote the antioxidant activity of GSH/GPX4 by causing reprogramming of ALF hepatocytes,thereby inhibiting hepatocyte ferroptosis.

关 键 词：解毒化瘀颗粒 ALF 铁死亡 GPX4 氧化应激 

分 类 号：R285.5[医药卫生—中药学]