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
刘美燕 1林镛 1黄小桃 1卢昌林 1刘志芳 1梅梦如 1陈炳东 1曹音 2毛德文 3龙富立3
作者信息
- 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;广西中医药防治医学分子生物重点实验室,广西南宁 530023
- 折叠
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(Fe2+)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.
Abstract
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 liv-er injury model,and different concentrations of JDHY drug-containing serum were co-cultured with the ALF liver damage mod-el,and the optimal concentration and co-culture time of JDHY were determined.Subsequently,the possible molecular mecha-nisms 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 ex-pression,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Key words
Detoxification and stasis granules/ALF/Iron death/GPX4/Oxidative stress引用本文复制引用
基金项目
国家自然科学基金(82260907)
国家自然科学基金(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)
出版年
2024
国家科技期刊平台
NSTL
万方数据