抗银屑病中药克银丸相关肝损伤的临床病例和实验评价  

Clinical cases and experimental evaluation of liver injury related to anti-psoriasis Keyin Pills

作　　者：熊鹏 陈帅帅 宋迪 朱敬肖 刘亚雷 郭玉明 柏兆方 赵海平[3] 王伽伯 肖小河 XIONG Peng;CHEN Shuai-shuai;SONG Di;ZHU Jing-xiao;LIU Ya-lei;GUO Yu-ming;BAI Zhao-fang;ZHAO Hai-ping;WANG Jia-bo;XIAO Xiao-he(School of Pharmacy,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;China Military Institute of Chinese Medicine,the Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China;School of Traditional Chinese Medicine,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学药学院,江西南昌330004 [2]中国人民解放军总医院第五医学中心全军中医药研究所,北京100039 [3]江西中医药大学中医学院,江西南昌330004

出　　处：《中国中药杂志》2020年第20期5017-5023,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81630100,81721002)。

摘　　要：克银丸是临床治疗银屑病的常用中成药,但有报道其可致严重肝损伤。该文采用整合证据链法,对药品不良反应数据库、CNKI文献及肝病专科医院的克银丸相关肝损伤病例进行检索及再评价,筛选出因果关系为可能及以上级别的病例共23例,其中单用克银丸且因果关系为肯定的病例有11例,占47.83%,提示克银丸致肝损伤客观存在。克银丸引起肝损伤的潜伏期跨度为1~90 d,累积服药剂量跨度为20~1 800 g,个体差异明显,未见肝损伤与剂量和疗程的依赖关系,提示克银丸致肝损伤具有特异质属性。进一步基于免疫应激介导的特异质肝损伤大鼠模型,证实了克银丸可在免疫应激模型大鼠剂量依赖地引起急性肝损伤,单次给药中毒剂量(14 g·kg-1)为临床等效剂量的6.7倍,而对正常大鼠肝功能生化指标及组织病理学均无显著影响。拆方实验表明,克银丸方中白鲜皮是致特异质肝损伤的主要药味,其他3味药既无肝损伤作用,也无配伍减毒作用。结果提示临床用药应重视克银丸对免疫应激状态患者可致肝损伤的风险。Keyin Pills is a kind of traditional Chinese medicine for the treatment of psoriasis, but it has been reported that it can cause serious liver injury. In this paper, we used the integrated evidence chain method to retrieve and reevaluate the adverse drug reaction database, CNKI literature and cases of liver injury relating to Keyin Pills in specialist hepatology hospitals. We screened out 23 cases with the causal relationship of the possible grade and above. Among them, 11 cases showed the positive causal relationship only with Keyin Pills, accounting for 47.83%, suggesting that there was objective liver injury caused by Keyin Pills. The incubation period of liver injury caused by Keyin Pills is 1-90 days, and the cumulative dosage span is 20-1 800 g. There were obvious individual diffe-rences. There was no relationship between liver injury as well as dose and course of treatment, suggesting that Keyin Pills could induce immune idiosyncratic liver injury. Furthermore, based on the liver injury model induced by immunological stress, it was confirmed that Keyin Pills could induce acute liver injury in a dose-dependent manner in rats with immunological stress. The toxic dose(14 g·kg-1) of a single dose was 6.7 times of the clinical equivalent dose, and had no significant effect on the biochemical index of liver function and histopathology in normal rats. Decomposition experiments showed that Dictamnus dasycarpus in Keyin Pills is the main medicinal flavor that causes special liver injury, and the other three medicines had neither liver injury nor compatibility attenuation effect. The results suggest that clinical medication shall pay attention to the risk of liver injury caused by Keyin Pills in patients with immunological stress.

关 键 词：药物性肝损伤 特异质 克银丸 免疫应激 白鲜皮 

分 类 号：R285.6[医药卫生—中药学]