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目的 探讨N-乙酰半胱氨酸(NAC)对大黄素(Emodin)所致肝损伤的保护作用及其可能机制。方法 体外实验使用毒性浓度(50 μmol/L)的大黄素处理HepG2细胞48 h，构建药物性肝损伤模型。NAC预处理细胞后，再加入50 μmol/L的大黄素，通过CCK-8法测定细胞活力，检测肝功能指标[谷丙转氨酶(ALT)、谷草转氨酶(AST)和乳酸脱氢酶(LDH)]及氧化应激指标[活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)]。体内实验使用SPF级C57BL/6小鼠，分为对照组、Emodin组、NAC组和Emodin+NAC组，连续给药3周后检测肝功能指标、氧化应激指标及肝组织病理学。通过STITCH 数据库分析大黄素的潜在靶点，采用RT-qPCR和Western blot法测定靶点的基因和蛋白表达水平。结果 50 μmol/L和100 μmol/L的大黄素显著降低HepG2细胞存活率，并诱导肝功能指标(ALT、AST和LDH)和氧化应激指标(ROS和MDA)升高，同时降低SOD和GSH水平。NAC干预后，细胞存活率显著提高，肝损伤指标和氧化应激水平明显降低。体内实验结果与体外一致，Emodin组小鼠肝损伤显著，表现为肝功能指标和氧化应激指标异常，而NAC显著逆转了这些变化。本研究发现细胞色素P450 1B1(CYP1B1)与大黄素肝损伤相关，大黄素诱导CYP1B1的表达，而NAC下调CYP1B1的表达。结论 大黄素可通过诱导CYP1B1表达和氧化应激而致肝损伤，NAC可能通过抑制CYP1B1/ROS通路改善大黄素诱导的肝细胞损伤，本研究可为探究大黄素肝毒性机制和解毒方法提供理论依据。
Abstract：Objective To determine the protective effect of N-acetylcysteine (NAC) on emodin-induced liver injury and its underlying mechanism.Methods In vitro experiments:we used the HepG2 cell line,to establish a liver injury model by treating cells with emodin for 48 h.The cells were pretreated with NAC before exposure to a toxic concentration (50 μmol/L) of emodin.Cell viability was determined with CCK-8 assay,and the liver function indicators including alanine aminotransferase (ALT),aspartate aminotransferase (AST),lactate dehydrogenase (LDH),as well as oxidative stress indicators such as reactive oxygen species (ROS),malondialdehyde (MDA),superoxide dismutase (SOD),and glutathione (GSH) were detected.In vivo experiments:C57BL/6 mice were divided into a control group,an Emodin group,an NAC group,and an Emodin+NAC group.After 3 weeks of continuous administration,liver function markers,oxidative stress indicators,and liver histopathology were evaluated.Potential targets of emodin were analyzed with the STITCH database.The mRNA and protein expression levels of these targets were detected with RT-qPCR and Western blot.Results Emodin at 50 μmol/L and 100 μmol/L greatly reduced HepG2 cell viability,increased the liver function markers (ALT,AST,and LDH) and oxidative stress indicators (ROS and MDA),and decreased SOD and GSH levels.NAC intervention greatly improved cell viability and markedly ameliorated the liver injury indicators and oxidative stress levels.Consistent with the in vitro results,mice in the Emodin group exhibited obvious liver injury,manifested by abnormal liver function markers and oxidative stress indicators,which were substantially reversed by NAC.CYP1B1 was associated with emodin-induced liver injury.Emodin induced CYP1B1 mRNA and protein expression,while NAC inhibited CYP1B1 expression.Conclusion Emodin may induce hepatotoxicity by upregulating CYP1B1 expression and promoting oxidative stress.NAC may ameliorate emodin-induced hepatocyte injury by inhibiting the CYP1B1/ROS pathway.This study provides a theoretical foundation for elucidating the mechanism of emodin-induced liver toxicity and detoxification strategies.
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基本信息:
中图分类号:R285
引用信息:
[1]吴莉莉,徐腾焱,庞佩珊,等.基于CYP1B1/ROS通路研究N-乙酰半胱氨酸对大黄素诱导的肝损伤的保护作用[J].中南药学,2026,24(04):28-34.
基金信息:
广东省基础与应用基础研究基金区域联合基金-青年基金项目(No.2023A1515110577); 广东省中医药局面上项目(No.20241299); 广东省医院药学研究基金(No.2024A18); 佛山市卫生健康局医学科研项目(No.20240146)
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