从传统非毒性中药肝毒性论临床个体化治疗(1)
[摘要] 中药的应用历史悠久，且被实践证明较安全有效。近年来，认识到服用西药所带来的毒副作用，更多的人转向对中药的关注和使用。由于中药是天然产物，除明确标明有毒性的如砒霜等，大多数即非传统毒性中药被大众误认为绝对安全，无毒副作用。然而，研究发现，临床应用中非传统毒性中药的毒性问题也不容忽视，尤其是中药肝毒性问题。相关研究发现，非传统毒性中药肝毒性与个体基因多态性以及体质密切相关。在查阅和分析大量有关中药致肝毒性文献及报道的基础上，该文旨在从临床应用角度探讨传统非毒性中药肝毒性产生的原因及机制，以期能够为中药的临床个体化给药提供新思路并指导中药临床的安全应用。
[关键词] 传统非毒性中药； 肝毒性； 系统生物学；生物转化
Individualized clinical treatment from the prospective of
hepatotoxicity of nontoxic traditional Chinese medicine
YANG Nan1，2， CHEN Juan1，2， HOU Xuefeng2， SONG Jie2， FENG Liang2， JIA Xiaobin1，2*
(1. Nanjing University of Chinese Medicine， Nanjing 210046， China；
2. Third School of Clinical Medical， Nanjing University of Chinese Medicine， Nanjing 210028， China)
[Abstract] Traditional Chinese medicine has a long history in clinical application， and been proved to be safe and effective. In recent years， the toxicity and sideeffects caused by the western medicine have been attracted much attention. As a result， increasing people have shifted their attention to traditional Chinese medicine. Nonetheless， due to the natural origin of traditional Chinese medicine and the lack of basic knowledge about them， many people mistakenly consider the absolute safety of traditional Chinese medicine， except for wellknown toxic ones， such as arsenic. However， according to the clinical practices and recent studies， great importance shall be attached to the toxicity of nontoxic traditional Chinese medicine， in particular the hepatotoxicity. Relevant studies indicated that the toxicity of nontoxic traditional Chinese medicine is closely correlated with individual gene polymorphism and constitution. By discussing the causes and mechanisms of the hepatotoxicity induced by nontoxic traditional Chinese medicine in clinical practices， we wrote this article with the aim to provide new ideas for individualized clinical therapy of traditional Chinese medicine and give guidance for rational and safe use of traditional Chinese medicine.
[Key words] nontoxic traditional Chinese medicine； hepatotoxicity； systems biology； bioconversion
doi：10.4268/cjcmm201617？？
藥物性肝损伤(DILI)是指临床用药过程中，由药物及其代谢产物的毒性反应导致的，或由于特异质体质对药物的超敏反应所致的肝损伤[12]。随着用药种类和不合理用药的日益增多，DILI 发病率、病死率不断增高。崔自慧等[3]发现药物性肝损伤大多由临床常用药引起，因此掌握药物的性能、药物的代谢机制、毒副作用等有重大意义。
中药肝损伤是指应用中药治疗疾病时引起的肝损伤。有关资料显示，约有100多种中草药和30多种中成药可引起药源性肝损伤[4]，中药导致的肝损伤占全部临床药物损伤的2.6%～4.8%[5]，为引起肝损伤的首位药物[68]。统计发现，中药肝损伤的主要临床表现为乏力、纳差、发热、瘙痒、恶心、黄疸、皮疹、呕吐及腹部不适，其分型主要有肝细胞型、胆汁淤积型和混合型[911]。 (杨楠 陈娟 侯雪峰 宋捷 封亮 贾晓斌)
[关键词] 传统非毒性中药； 肝毒性； 系统生物学；生物转化
Individualized clinical treatment from the prospective of
hepatotoxicity of nontoxic traditional Chinese medicine
YANG Nan1，2， CHEN Juan1，2， HOU Xuefeng2， SONG Jie2， FENG Liang2， JIA Xiaobin1，2*
(1. Nanjing University of Chinese Medicine， Nanjing 210046， China；
2. Third School of Clinical Medical， Nanjing University of Chinese Medicine， Nanjing 210028， China)
[Abstract] Traditional Chinese medicine has a long history in clinical application， and been proved to be safe and effective. In recent years， the toxicity and sideeffects caused by the western medicine have been attracted much attention. As a result， increasing people have shifted their attention to traditional Chinese medicine. Nonetheless， due to the natural origin of traditional Chinese medicine and the lack of basic knowledge about them， many people mistakenly consider the absolute safety of traditional Chinese medicine， except for wellknown toxic ones， such as arsenic. However， according to the clinical practices and recent studies， great importance shall be attached to the toxicity of nontoxic traditional Chinese medicine， in particular the hepatotoxicity. Relevant studies indicated that the toxicity of nontoxic traditional Chinese medicine is closely correlated with individual gene polymorphism and constitution. By discussing the causes and mechanisms of the hepatotoxicity induced by nontoxic traditional Chinese medicine in clinical practices， we wrote this article with the aim to provide new ideas for individualized clinical therapy of traditional Chinese medicine and give guidance for rational and safe use of traditional Chinese medicine.
[Key words] nontoxic traditional Chinese medicine； hepatotoxicity； systems biology； bioconversion
doi：10.4268/cjcmm201617？？
藥物性肝损伤(DILI)是指临床用药过程中，由药物及其代谢产物的毒性反应导致的，或由于特异质体质对药物的超敏反应所致的肝损伤[12]。随着用药种类和不合理用药的日益增多，DILI 发病率、病死率不断增高。崔自慧等[3]发现药物性肝损伤大多由临床常用药引起，因此掌握药物的性能、药物的代谢机制、毒副作用等有重大意义。
中药肝损伤是指应用中药治疗疾病时引起的肝损伤。有关资料显示，约有100多种中草药和30多种中成药可引起药源性肝损伤[4]，中药导致的肝损伤占全部临床药物损伤的2.6%～4.8%[5]，为引起肝损伤的首位药物[68]。统计发现，中药肝损伤的主要临床表现为乏力、纳差、发热、瘙痒、恶心、黄疸、皮疹、呕吐及腹部不适，其分型主要有肝细胞型、胆汁淤积型和混合型[911]。 (杨楠 陈娟 侯雪峰 宋捷 封亮 贾晓斌)