黄芩苷治疗药物性肝损伤的作用机制探讨——基于网络药理学和实验验证
Journal: Frontiers of Chinese Medicine Research DOI: 10.12238/fcmr.v7i2.14515
Abstract
目的：结合体内实验与网络药理学,系统阐明黄芩苷改善药物性肝损伤的作用机制。方法：建立阿托伐他汀诱导DILI动物模型,检测小鼠血清丙氨酸转氨酶与天冬氨酸转氨酶水平。应用网络药理学方法搜集黄芩苷、DILI相关靶点,通过韦恩映射筛选交集靶点,构建PPI,进而进行GO功能与京都基因与KEGG通路富集分析。结果：体内实验结果显示黄芩苷可显著减少小鼠血清ALT与AST水平；网络药理学实验结果显示TCMSP、pubchem、Pharmmapper数据库共搜集到黄芩苷相关靶点436个；Genecards、OMIM数据库共搜集到DILI相关靶点10905个；Venny2.1.0数据库共筛选出175个交集靶点；PPI网络中度值排名前10的核心靶点依次为IL2、GSK3B、APP、SORD、ALDH1A1、DHFR、AKR1B1、PLG、CDC42、PRKACA；GO分析富集到异生物质代谢过程、蛋白质结合、细胞外外泌体等,KEGG分析得到代谢途径、化学致癌-活性氧等信号通路。结论：黄芩苷可能通过调控多个靶点及相关信号通路发挥抗DILI作用,本研究为其机制研究提供了理论支持。
Keywords
黄芩苷；阿托伐他汀；药物性肝损伤；网络药理学
Funding
浙江省药品监督管理局科技计划项目“Nrf2激活剂黄芩苷对药物性肝损伤的作用研究”(2023023)；浙江省医药卫生科技计划项目(2025KY1442)；浙江省教育厅一般科研项目(Y202456612)。
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