广东药科大学学报2026，Vol.42Issue(2)：64-76,13.DOI:10.16809/j.cnki.2096-3653.2026011902
基于网络毒理学和动物实验研究苦参碱的肝毒性机制
Study on the hepatotoxicity mechanism of matrine based on network toxicology and animal experiments
摘要
Abstract
Objective To explore the mechanism of matrine hepatotoxicity based on network toxicology and animal experiments.Methods The TCMS and CTD databases were used to collect the targets of matrine hepatotoxicity,and the GeneCards database was used to obtain the targets related to hepatotoxic diseases.The intersection targets of the two sets were taken and uploaded to the STRING database to construct the target interaction map.The DAVID(https://david.ncifcrf.gov/home.jsp)database was used for GO functional annotation analysis and KEGG pathway enrichment analysis,and molecular docking was performed.The mice were randomly divided into a negative control group,a matrine group(200 mg/kg),and an acetaminophen group(300 mg/kg),with 10 mice in each group,and received a single gavage administration.In vivo experiments were conducted to verify the levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),lactate dehydrogenase(LDH),superoxide dismutase(SOD),and glutathione(GSH)through HE staining and DAPI staining.The mRNA expression levels of genes such as TNF and IL-6 in liver tissues were detected using qPCR.Results A total of 130 matrine and hepatotoxicity intersection targets were screened out by network toxicology.A total of 165 pathways were enriched by KEGG,involving the release of inflammatory mediators,TNF signaling pathway,TGF-β1 signaling pathway,etc.Molecular docking showed that matrine had good affinity for core genes such as TNF.The results of animal experiments showed that the contents of SOD and GSH in the matrine group were significantly decreased(P<0.05 or P<0.01),and the liver tissue was significantly damaged.The results of qPCR further showed that matrine significantly upregulates the expression of TNF,IL-6,TGF-β1,TP53 and NOS2 genes,and downregulates the expression of NQO1 gene.The results showed that matrine may induce oxidative stress and induce apoptosis.Conclusion Matrine-induced hepatotoxicity is the result of multi-target and multi-pathway synergistic regulation,and its molecular mechanism may be related to the abnormal regulation of TNF and TGF-β1 signaling pathways,which in turn mediates hepatocyte damage,inflammatory response,and pathological changes in liver tissue.关键词
苦参碱/肝毒性/网络毒理学/分子对接/TNF信号通路/TGF-β1信号通路Key words
matrine/hepatotoxicity/network toxicology/molecular docking/TNF signaling pathway/TGF-β1 signaling pathway分类
医药卫生引用本文复制引用
张红妹,陈杰君,杜青云,杨仁轩,吴俊标,郭秋平..基于网络毒理学和动物实验研究苦参碱的肝毒性机制[J].广东药科大学学报,2026,42(2):64-76,13.基金项目
广东省自然科学基金项目(2024A1515012010) （2024A1515012010）
