免疫调控与特异质型药物性肝损伤发生机制研究进展  

Progress in research on the pathogenesis of immune regulation and idiosyncratic drug-induced liver injury

作　　者：柏兆方[1] 高源[1,2] 左晓彬 王伽伯[1] 肖小河[3] 

机构地区：[1]解放军302医院全军中医药研究所,北京100039 [2]北京中医药大学中药学院,北京100029 [3]解放军302医院中西医结合诊疗与研究中心,北京100039

出　　处：《药学学报》2017年第7期1019-1026,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金青年基金资助项目(81503350);国家自然科学基金重点资助项目(81630100);国家"重大新药创制"科技重大专项课题(2015ZX09501-004-001-008);国家公益性行业科研专项课题(201507004-04)

摘　　要：特异质型药物性肝损伤(idiosyncratic drug-induced liver injury,IDILI)是仅在少数人群发生的药物不良反应,其发生往往与服药时间、剂量无明确对应关系,具有不可预测性和发病率低等特点。研究表明,IDILI是机体、环境和药物因素协同作用的结果,而机体免疫是IDILI发生的主要诱因。目前,化学药物诱导的IDILI研究较为广泛和深入,形成了多种免疫学机制假说,较好地阐释了其发病特点和机制。近年来,中药特异质肝损伤也逐步被证实,并且形成了中药特异质肝损伤免疫应激"三因致毒"机制假说,较为全面地揭示了中药IDILI的发病特点和机制。本文就化学药物和中药诱导的IDILI免疫学机制假说进行综述,以期为IDILI评价和临床风险防控对策建立提供科学依据。Idiosyncratic drug-induced liver injury（IDILI） is an adverse drug reaction that occurs only in a minority of the population. IDILI also has many characteristics such as unpredictable and low morbidity, its occurrence has often not been clearly correlated with the dose, route, or duration of drug administration. Several studies have shown that IDILI is a synergistic effect which was caused by body diathesis, environment and drugs. In addition, evidence also suggests that most IDILIs are mediated by immunity. Chemical medicines-related IDILIs have been extensively studied, and a variety of immunological mechanism hypotheses have also emerged to explain the pathogenesis and characteristics of chemical medicines-related IDILIs. However, the traditional Chinese medicine（TCM）-related IDILI has always been neglected due to the complexity and specificity of TCM. In recent years, TCM-related IDILI has been gradually confirmed by researchers, and formed a new hypothesis, a immunological stress-mediated tri-elements synergetic mechanism hypothesis, which can reveal the pathogenesis and clinical characteristics of TCM-related IDILI. This paper is prepared to summarize the immunological mechanism hypotheses of chemical medicine-related IDILI and TCM-related IDILI to provide a scientific basis for guiding IDILI research and establishing its clinical risk prevention and control measures.

关 键 词：特异质型药物性肝损伤 免疫调控 化学药物 中药 机制假说 

分 类 号：R969.3[医药卫生—药理学]