基于中药特点的肝毒性研究与思考

Research and considerations on hepatotoxicity based on characteristics of Chinese materia medica

中药的安全性是临床应用的关键因素。肝脏作为药物代谢的重要场所,也是药物毒性反应的主要靶器官之一。中药毒性与药性、体质、配伍等密切相关。中药肝毒性的作用机制涉及氧化应激、线粒体损伤、炎症反应、胆汁淤积、能量及糖脂代谢紊乱、肝药酶影响等,且因中药成分复杂,具有多途径、多靶点作用,加之药物成分间相互作用等影响因素,导致中药毒性研究和安全性评价存在诸多问题。中药安全性评价应结合中药的特点,排除农药残留、重金属、真菌等外源性污染因素,并重视同名异物、产地与种植条件、炮制、配伍等源于中药自身因素的影响。近年来,中药肝毒性研究采用结构预警预测肝毒性成分,加强离体与整体实验、药代与毒代综合分析,并结合运用系统毒理学等新理论、新技术与新方法进行精准评价,为临床用药安全提供更全面的参考。

The safety of Chinese materia medica is the key factor of clinical application. As an important place of drug metabolism, liver is also one of the main target organs of drug toxicity. The toxicity of Chinese materia medica is closely related to its properties, body constitution and compatibility. The mechanisms of hepatotoxicity of Chinese materia medica involve oxidative stress, mitochondrial damage, inflammatory reaction, cholestasis, disorder of energy and glycolipid metabolism, and influence of hepatic drug enzyme. There are many problems in toxicity research and safety evaluation of Chinese materia medica due to its complex components, multi-pathways and multi-targets, and interaction among drug ingredients. The safety evaluation of Chinese materia medica should be combined with the characteristics of Chinese materia medica, eliminate the external pollution factors such as pesticide residues, heavy metals and fungi, and pay attention to the influence of self-factors of Chinese materia medica, such as homonym, origin and planting conditions, processing and compatibility. In recent years, structural early warning is used in the study of hepatotoxicity of Chinese materia medica to predict the hepatotoxic components. The comprehensive analysis of the experiment in vivo and in vitro and the pharmaco-and toxic-kinetics are emphasized. Combined with the application of new theories, technologies and methods, such as systems toxicology, the accurate evaluation is achieved, which provides more comprehensive reference for clinical medication safety.