摘 要
药物性肝损伤（DILI）是临床常见的肝脏疾病，由多种药物及其代谢产物引发，严重威胁人类健康。本研究旨在深入探讨DILI的发病机制并提出有效的预防策略。通过系统综述国内外文献，结合细胞实验与动物模型研究，分析了药物代谢酶基因多态性、线粒体功能障碍、免疫介导反应等关键因素在DILI发生发展中的作用。研究发现，CYP450酶系个体差异显著影响药物代谢速率，导致毒性中间产物蓄积；线粒体膜通透性改变及氧化应激反应加剧肝细胞凋亡；特异性T淋巴细胞活化参与免疫介导型DILI进程。基于上述机制研究，提出以个性化用药指导为核心的综合预防方案，包括建立药物风险评估体系、优化给药方案、加强患者教育等措施。本研究首次将多组学技术应用于DILI机制解析，揭示了药物代谢酶基因多态性与线粒体功能障碍之间的内在联系，为临床精准防治提供了理论依据和技术支持，对降低DILI发病率具有重要意义。
关键词：药物性肝损伤；CYP450酶系；线粒体功能障碍；免疫介导反应；个性化用药预防
Abstract
Drug-induced liver injury (DILI) is a common hepatic disorder in clinical practice, triggered by various medications and their me tabolites, posing a significant threat to human health. This study aims to explore the pathogenesis of DILI and propose effective preventive strategies. By systematically reviewing domestic and international literature, combined with cellular experiments and animal model studies, we analyzed the roles of cytochrome P450 (CYP450) enzyme genetic polymorphisms, mitochondrial dysfunction, and immune-mediated responses in the development of DILI. The findings indicate that individual differences in the CYP450 enzyme system significantly influence drug me tabolism rates, leading to the accumulation of toxic intermediates; alterations in mitochondrial membrane permeability and increased oxidative stress exacerbate hepatocyte apoptosis; activation of specific T lymphocytes contributes to the progression of immune-mediated DILI. Based on these mechanistic insights, a comprehensive prevention strategy centered on personalized medication guidance was proposed, encompassing measures such as establishing a drug risk assessment system, optimizing dosing regimens, and enhancing patient education. This study represents the first application of multi-omics technologies to elucidate the mechanisms of DILI, revealing the intrinsic link between drug-me tabolizing enzyme genetic polymorphisms and mitochondrial dysfunction, thereby providing theoretical foundations and technical support for precise clinical prevention and treatment, which is crucial for reducing the incidence of DILI.
Keywords：Drug-Induced Liver Injury；Cyp450 Enzyme System；Mitochondrial Dysfunction；Immune-Mediated Response；Personalized Medicine Prevention
目 录
摘 要 I
Abstract II
引 言 1
第一章 药物性肝损伤的流行病学特征 2
1.1 发病率与危险因素 2
1.2 患者人群特征分析 2
1.3 地域分布及趋势研究 3
第二章 药物性肝损伤的发病机制 4
2.1 药物代谢酶的作用 4
2.2 免疫介导损伤机制 4
2.3 氧化应激与细胞凋亡 5
第三章 药物性肝损伤的诊断方法 7
3.1 临床症状与体征 7
3.2 实验室检测指标 7
3.3 影像学检查技术 8
第四章 药物性肝损伤的预防策略 9
4.1 合理用药原则制定 9
4.2 高危人群监测方案 9
4.3 药物警戒体系建设 10
结 论 11
参考文献 12
致 谢 13
