中药药源性肝损伤评价方法及风险因素研究进展
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摘要
近年来中药药源性肝损伤事件屡见报道,引起医药界、制药业、管理部门及公众的高度关注。由于药源性肝损伤(drug-induced liver injury,DILI)缺少特异性诊断指标,加上中药自身的复杂性,使得中药相关DILI的评价更加困难,是国内外研究的重点和难点。本文基于以临床评价证据为主导的原则,结合国家不良反应监测中心通报及Liver Tox网站收录数据对文献及相关报道中的常见可疑损肝中药进行综合评述。在此基础上,对比国内外主要不良反应或肝损伤评价方法的差异性和适用性,重点对国家药品监督管理局近期发布的《中药药源性肝损伤临床评价技术指导原则》中的中药相关DILI评价方法进行解读。最后,分别从药物因素、患者因素、不合理用药等方面对中药相关DILI的风险因素进行综述。本文为认识和评价中药相关DILI的客观真实性、发展符合中药特点的DILI评价方法体系和风险防控体系提供了一些新的观点,以期为降低中药药源性肝损伤的发生提供参考。
In recent years,the occurrence of Chinese medicines(CM)-induced liver injury has been reported frequently,which has attracted high attention of the medical field,pharmaceutical industry,government department,etc.Due to the lack of specific diagnostic indicators of drug-induced liver injury(DILI)and the complexity of CM,the evaluation of CM-induced liver injury is becoming more difficult,which is the focus and difficulty in research all over the world.Based on the principle of taking clinical evaluation evidence as the leading role,and combined with the reporting of national ADR center and Liver Tox website,a comprehensive review,the common CM suspected of causing liver injury in the literature and related reports,would be made in this paper.Based on it,we analyze the differences and applicability of evaluation methods of major adverse reactions(liver injury)between domestic and overseas literature,especially focusing on interpreting the evaluation method of CM-induced liver injury from the clinical evaluation of CM-induced liver injury issued by the China Food and Drug administration.Finally,the risk factors of CM-induced liver injury,such as drugs,patients,unreasonable drug use and so on,could be summarized.This paper provides some new ideas for cognition and assessment of the objectivity and authenticity of CM-induced liver injury,and for developing the system of evaluating DILI along with its risk prevention and control consistent with the characteristics of CM,which contributes to reduce the occurrence of CM-induced liver injury for reference.
In recent years,the occurrence of Chinese medicines(CM)-induced liver injury has been reported frequently,which has attracted high attention of the medical field,pharmaceutical industry,government department,etc.Due to the lack of specific diagnostic indicators of drug-induced liver injury(DILI)and the complexity of CM,the evaluation of CM-induced liver injury is becoming more difficult,which is the focus and difficulty in research all over the world.Based on the principle of taking clinical evaluation evidence as the leading role,and combined with the reporting of national ADR center and Liver Tox website,a comprehensive review,the common CM suspected of causing liver injury in the literature and related reports,would be made in this paper.Based on it,we analyze the differences and applicability of evaluation methods of major adverse reactions(liver injury)between domestic and overseas literature,especially focusing on interpreting the evaluation method of CM-induced liver injury from the clinical evaluation of CM-induced liver injury issued by the China Food and Drug administration.Finally,the risk factors of CM-induced liver injury,such as drugs,patients,unreasonable drug use and so on,could be summarized.This paper provides some new ideas for cognition and assessment of the objectivity and authenticity of CM-induced liver injury,and for developing the system of evaluating DILI along with its risk prevention and control consistent with the characteristics of CM,which contributes to reduce the occurrence of CM-induced liver injury for reference.
引文
[1] 于乐成,茅益民,陈成伟.药物性肝损伤诊治指南[J].临床肝胆病杂志,2015,31(11):1752-1769.
[2] 张力,杨晓晖,孙震晓,等.何首乌临床不良事件回顾性研究及风险控制措施探讨[J].中国中药杂志,2009,34(13):1724-1729.
[3] WANG J B,MA Z J,NIU M,et al.Evidence Chain-Based Causality Identification for Herb-induced Liver Injury:Exemplification of a Fa-mous Liver-restorative Herb Polygonum Multiflorum[J].Front of Med,2015,9:457-467.
[4] 国家药品监督管理局.中药药源性肝损伤临床评价技术指导原则[EB/OL].(2018-06-12)[2018-06-12].http://www.nmpa.gov.cn/WS04/CL2182/229510.html
[5] Hoofnagle J H,Serrano J,Knoben J E,et al.Liver Tox:a website on drug-induced liver injury[J].Hepatology,2013,57:873.
[6] 李奇,赵奎君,赵艳玲,等.大剂量何首乌醇提物致大鼠多脏器损伤研究[J].环球中医药,2013,6(1):1-7.
[7] 张乐,柏兆方,李春雨,等.制首乌中顺式二苯乙烯苷转化量与特异质肝损伤的相关性研究[J].药学学报,2017,52(7):1041-1047.
[8] 国家药品不良反应监测中心.药品不良反应信息通报[J].中国药物警戒,2009,6(1):55-56.
[9] 张林,张晶璇,范琼尹,等.均匀设计结合多元回归分析用于淫羊藿对大鼠肝毒性的影响[J].中国实验方剂学杂志,2018,24(6):189-197.
[10] 平键,陈红云,张晶,等.淫羊藿苷干预核因子NF-κB抑制肝星状细胞活化的研究[J].辽宁中医杂志,2013,40(11):2188-2191.
[11] 宋晓静.壮骨关节丸致肝损害一例[J].中外医疗,2009,28(18):181.
[12] 药品不良反应信息通报:警惕壮骨关节丸引起的肝损害[J].中国执业药师,2008,5(11):19-20.
[13] 王雨,林志健,王笑,等.含补骨脂中成药肝损伤案例的分析与警戒思考[J].中国药物警戒,2018,15(5):300-303.
[14] 李颖君,黄吟月.补骨脂致药物性肝损伤一例[J].上海医药,2016,37(24):41-42.
[15] 张玥,毕亚男,袁晓美,等.基于靶器官的补骨脂肝毒性成分探讨[J].时珍国医国药,2017,28(8):1844-1847.
[16] 吴豪,宋捷,仲青香,等.基于斑马鱼模型研究补骨脂肝损伤效应及作用机制[J].南京中医药大学学报,2017,33(3):263-267.
[17] 黄奕雪,郭玉明,周永峰,等.基于整合证据链的白鲜皮粉末致肝损伤病例实验研究[J].中国中药杂志,2017,42(3):600-606.
[18] 刘宇翰,周雨燕,孙慧敏,等.白鲜皮导致药物性肝损伤的病理学及血清酶学改变[J].中国当代医药,2017,24(26):7-11.
[19] 王晓萌,林晓兰,张鹏.38例何首乌致肝损害的原因分析[J].北京中医药,2014,33(9):699-701.
[20] 雷飞,杨定权,甘超男,等.何首乌制剂致急性肝损伤1例[J].世界中西医结合杂志,2015,10(1):114-115,117.
[21] 丁斯斯,熊焰.中药土三七致肝小静脉闭塞症1例报告[J].中西医结合肝病杂志,2018,28(1):61-62.
[22] 李康艳,李颖霞,刘政和,等.肝窦阻塞综合征80例临床特点分析[J].河南医学研究,2018(10):1-3.
[23] 苟小军,曹健美,侯立新.土三七诱导肝小静脉闭塞病大鼠模型研究[J].上海中医药大学学报,2017,31(5):86-90,101.
[24] 王少珍,廖联明.黄药子中毒导致肝损伤的机制研究[J].中华卫生应急电子杂志,2018,4(1):33-44.
[25] 黄智锋,华碧春,陈小峰,等.黄药子及其制剂致肝损害78例临床分析[J].中国实验方剂学杂志,2013,19(23):295-297.
[26] 马丽琴.黄药子导致急性肝损害猝死一例[C]//浙江省医学会病理学分会.2013年浙江省病理学术年会论文汇编.宁波:浙江省医学会病理学分会,2013:1.
[27] 陈莹蓉,王翔,闵丽姗,等.黄药子醇提物Caco-2细胞摄取液对HL-7702和HepG2细胞毒性研究[J].中国现代应用药学,2013,30(4):368-372.
[28] 杨睿.千里光碱致肝细胞毒性机制初探[C]//中国毒理学会中药与天然药物毒理专业委员会.中国毒理学会中药与天然药物毒理专业委员会第一次(2016年)学术交流大会论文集.天津:中国毒理学会中药与天然药物毒理专业委员会,2016:1.
[29] 王秀坤.千里光肝脏毒性研究[D].北京:中国中医科学院,2008.
[30] 夏启松,张晓鸣,韩凤梅,等.千里光致小鼠肝损伤的基因表达谱分析[J].中国药学杂志,2007,42(20):1529-1533.
[31] 朱春烁,关帅,宋畅.雷公藤多甙片致急性肝损伤1例[J].中国现代药物应用,2018,12(13):164-165.
[32] 周文静,柴智,李艳彦,等.归脾汤对雷公藤醇提物致肝损伤大鼠肝细胞线粒体保护作用[J].山西中医学院学报,2018,19(4):24-26,29.
[33] 张靖,胡骞,谭亲友,等.甘草提取物对雷公藤甲素损伤后人肝L-02细胞中UGT1A、MRP2表达的影响[J].中国药房,2018,29(1):65-68.
[34] 姚云洁,肖朗,杨才兴,等.中草药所致DILI患者临床和肝组织病理学特点分析[J].实用肝脏病杂志,2016,19(4):441-444.
[35] 马进,陈岷.鸦胆子油乳注射液不良反应38例回顾性分析[J].中国中医药信息杂志,2014,21(4):116-117.
[36] 梁晶.鸦胆子油乳致肝损害9例临床分析[J].安徽医药,2007(1):93-94.
[37] 王艳辉,赵海平,王伽伯,等.基于“有故无殒”思想的熟大黄对肝脏量-毒/效关系研究[J].中国中药杂志,2014,39(15):2918-2923.
[38] 陈颖,王茉,景莉君,等.基于斑马鱼模型筛选壮骨关节丸毒性药味高效筛选[J].世界科学技术—中医药现代化,2017,19(1):133-141.
[39] 邓培媛,蔡皓东,程经华,等.壮骨关节丸致肝损害30例报告[J].中国新药杂志,1996(3):212-214.
[40] 宋晓静.壮骨关节丸致肝损害一例[J].中外医疗,2009,28(18):181.
[41] 唐进法,王晓艳,温强,等.免疫应激介导的壮骨关节丸致特异质肝损伤评价[J].药学学报,2017,52(7):1033-1040.
[42] 唐进法,王晓艳,杨伟,等.基于统计建模的壮骨关节丸诱发特异质肝损伤相关易感性细胞因子分析[J].药学学报,2018,53(4):574-584.
[43] 赵敏,孙瑞芳,黄坤.骨康胶囊致药物性肝炎1例[J].中国药物警戒,2016,13(1):55-56.
[44] 朱兰,逄瑜,杨乐,等.骨康胶囊肝损伤风险特点及因素分析[J].中国药物警戒,2018,15(4):248-250,256.
[45] 唐鸿珊,常立非.复方青黛丸引起肝损害2例[J].皮肤病与性病,1995(3):73-74.
[46] 倪晓珺,程能能.痔血胶囊组方对原代培养大鼠肝细胞和小鼠肝脏的毒性[J].中国临床药学杂志,2010,19(5):271-275.
[47] 李品,王琦,彭莉,等.痔血胶囊水提物和醇提物对大鼠肝毒性的影响[J].中国实验方剂学杂志,2017,23(8):154-159.
[48] 王晓今,陈成伟,傅青春,等.痔血胶囊单药致群发性肝损伤——附30例分析[J].肝脏,2009,14(4):287-290.
[49] 黄晨,朱光辉,王增寿,等.痔血胶囊致肝损害1例[J].中国临床药学杂志,2009,18(3):173-174.
[50] 张秋玲,杨佳,卢奕霞.白蚀丸致肝损害[J].药物不良反应杂志,2010,12(4):297-298.
[51] 魏戌,谢雁鸣.国内外不良反应因果判断原则及评价方法解读[J].中国中药杂志,2012,37(18):2744-2747.
[52] DANAN G,BENICHOU C.Causality assessment of adverse reactions to drugs--I.A novel method based on the conclusions of international consensus meetings:application to drug-induced liver injuries[J].J Clin Epidemiol,1993,46(11):1323-1330.
[53] ROCKEY D C,SEEFF L B,ROCHON J,et al.Causality Assessment in Drug-Induced Liver Injury Using a Structured Expert Opinion Process:Comparison to the Roussel-Uclaf Causality Assessment Method[J].Hepatology,2010,51(6):2117-2126.
[54] 王伽伯,张乐,郭玉明,等.中药药源性肝损伤因果关系的评价策略和方法[J].药学学报,2018,53(6):920-928.
[55] 肖小河,李秀惠,朱云,等.中草药相关肝损伤临床诊疗指南[J].临床肝胆病杂志,2016,32(5):835-843.
[56] NAVARRO V J,LUCENA M I.Hepatotoxicity induced by herbal and dietary supplements[J].Semin Liver Dis,2014,34:172-193.
[57] TESCHKE R,FRENZEL C,GLASS X,et al.Herbal hepatotoxicity:a critical review[J].Br J Clin Pharmacol,2013,75:630-636.
[58] 王秀坤,赵雍,梁爱华,等.不同产地千里光急性毒性实验研究[J].药物不良反应杂志,2008(2):81-85.
[59] 涂灿,蒋冰倩,赵艳玲,等.何首乌炮制前后对大鼠肝脏的损伤比较及敏感指标筛选[J].中国中药杂志,2015,40(4):654-660.
[60] 李春雨,何琴,唐进法,等.免疫应激介导的何首乌“九蒸九晒”炮制减毒作用及代谢组学研究[J].药学学报,2017,52(7):1069-1076.
[61] 王伽伯,马永刚,金城,等.对应分析在大黄炮制减毒“量-毒”规律研究中的应用[J].中国中药杂志,2009,34(19):2498-2502.
[62] 葛斐林,牛明,韩紫欣,等.白鲜皮制剂相关肝损伤的药物流行病学特征分析[J/OL].中国中药杂志,2018,https://doi.org/10.19540/j.cnki.cjmm.20181217.001.
[63] HE L,YIN P,MENG Y,et al.Immunological synergistic mechanisms of trans-/cis-stilbene glycosides in Heshouwu-related idiosyncratic liver injury[J].Sci.Bull,2017(11):748-751.
[64] Li C Y,Niu M,Bai Z F,et al.Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb,Polygonum multiflorum[J].Front Med,2017,11(2):253-265.
[65] 杨连梅.中药处方点评分析[J].光明中医,2018,33(14):1993-1995.
[66] 庞晶瑶,李雨萌,柏兆方,等.基于高内涵分析的何首乌对肝窦内皮细胞损伤的配伍减毒研究[J].中国现代中药,2015,17(4):331-334.
[67] 杨倩.柴胡挥发油肝毒性“量-时-毒”关系研究[D].济南:山东中医药大学,2011.
[68] 高素强,胡咏川.中药注射剂的应用现状与上市后再评价[J].中国中药杂志,2007,32(13):1370-1372.
[69] 孙学东.应该重视中西药相互不良作用[J].中药新药与临床药理,1997,8(4):9-10.
[70] 牟萍,兰伯恩,吴孟轩.医院81例严重药品不良反应/不良事件报告分析[J].中国药业,2016,25(12):85-88.
[71] 师建平,郭静.中医辨证论治理论体系的研究现状与发展趋势[J].中华中医药杂志,2013,28(9):2508-2510.
[72] 王伽伯,李春雨,朱云,等.基于整合证据链的中草药肝毒性客观辨识与合理用药:以何首乌为例[J].科学通报,2016,61(9):971-980.
[2] 张力,杨晓晖,孙震晓,等.何首乌临床不良事件回顾性研究及风险控制措施探讨[J].中国中药杂志,2009,34(13):1724-1729.
[3] WANG J B,MA Z J,NIU M,et al.Evidence Chain-Based Causality Identification for Herb-induced Liver Injury:Exemplification of a Fa-mous Liver-restorative Herb Polygonum Multiflorum[J].Front of Med,2015,9:457-467.
[4] 国家药品监督管理局.中药药源性肝损伤临床评价技术指导原则[EB/OL].(2018-06-12)[2018-06-12].http://www.nmpa.gov.cn/WS04/CL2182/229510.html
[5] Hoofnagle J H,Serrano J,Knoben J E,et al.Liver Tox:a website on drug-induced liver injury[J].Hepatology,2013,57:873.
[6] 李奇,赵奎君,赵艳玲,等.大剂量何首乌醇提物致大鼠多脏器损伤研究[J].环球中医药,2013,6(1):1-7.
[7] 张乐,柏兆方,李春雨,等.制首乌中顺式二苯乙烯苷转化量与特异质肝损伤的相关性研究[J].药学学报,2017,52(7):1041-1047.
[8] 国家药品不良反应监测中心.药品不良反应信息通报[J].中国药物警戒,2009,6(1):55-56.
[9] 张林,张晶璇,范琼尹,等.均匀设计结合多元回归分析用于淫羊藿对大鼠肝毒性的影响[J].中国实验方剂学杂志,2018,24(6):189-197.
[10] 平键,陈红云,张晶,等.淫羊藿苷干预核因子NF-κB抑制肝星状细胞活化的研究[J].辽宁中医杂志,2013,40(11):2188-2191.
[11] 宋晓静.壮骨关节丸致肝损害一例[J].中外医疗,2009,28(18):181.
[12] 药品不良反应信息通报:警惕壮骨关节丸引起的肝损害[J].中国执业药师,2008,5(11):19-20.
[13] 王雨,林志健,王笑,等.含补骨脂中成药肝损伤案例的分析与警戒思考[J].中国药物警戒,2018,15(5):300-303.
[14] 李颖君,黄吟月.补骨脂致药物性肝损伤一例[J].上海医药,2016,37(24):41-42.
[15] 张玥,毕亚男,袁晓美,等.基于靶器官的补骨脂肝毒性成分探讨[J].时珍国医国药,2017,28(8):1844-1847.
[16] 吴豪,宋捷,仲青香,等.基于斑马鱼模型研究补骨脂肝损伤效应及作用机制[J].南京中医药大学学报,2017,33(3):263-267.
[17] 黄奕雪,郭玉明,周永峰,等.基于整合证据链的白鲜皮粉末致肝损伤病例实验研究[J].中国中药杂志,2017,42(3):600-606.
[18] 刘宇翰,周雨燕,孙慧敏,等.白鲜皮导致药物性肝损伤的病理学及血清酶学改变[J].中国当代医药,2017,24(26):7-11.
[19] 王晓萌,林晓兰,张鹏.38例何首乌致肝损害的原因分析[J].北京中医药,2014,33(9):699-701.
[20] 雷飞,杨定权,甘超男,等.何首乌制剂致急性肝损伤1例[J].世界中西医结合杂志,2015,10(1):114-115,117.
[21] 丁斯斯,熊焰.中药土三七致肝小静脉闭塞症1例报告[J].中西医结合肝病杂志,2018,28(1):61-62.
[22] 李康艳,李颖霞,刘政和,等.肝窦阻塞综合征80例临床特点分析[J].河南医学研究,2018(10):1-3.
[23] 苟小军,曹健美,侯立新.土三七诱导肝小静脉闭塞病大鼠模型研究[J].上海中医药大学学报,2017,31(5):86-90,101.
[24] 王少珍,廖联明.黄药子中毒导致肝损伤的机制研究[J].中华卫生应急电子杂志,2018,4(1):33-44.
[25] 黄智锋,华碧春,陈小峰,等.黄药子及其制剂致肝损害78例临床分析[J].中国实验方剂学杂志,2013,19(23):295-297.
[26] 马丽琴.黄药子导致急性肝损害猝死一例[C]//浙江省医学会病理学分会.2013年浙江省病理学术年会论文汇编.宁波:浙江省医学会病理学分会,2013:1.
[27] 陈莹蓉,王翔,闵丽姗,等.黄药子醇提物Caco-2细胞摄取液对HL-7702和HepG2细胞毒性研究[J].中国现代应用药学,2013,30(4):368-372.
[28] 杨睿.千里光碱致肝细胞毒性机制初探[C]//中国毒理学会中药与天然药物毒理专业委员会.中国毒理学会中药与天然药物毒理专业委员会第一次(2016年)学术交流大会论文集.天津:中国毒理学会中药与天然药物毒理专业委员会,2016:1.
[29] 王秀坤.千里光肝脏毒性研究[D].北京:中国中医科学院,2008.
[30] 夏启松,张晓鸣,韩凤梅,等.千里光致小鼠肝损伤的基因表达谱分析[J].中国药学杂志,2007,42(20):1529-1533.
[31] 朱春烁,关帅,宋畅.雷公藤多甙片致急性肝损伤1例[J].中国现代药物应用,2018,12(13):164-165.
[32] 周文静,柴智,李艳彦,等.归脾汤对雷公藤醇提物致肝损伤大鼠肝细胞线粒体保护作用[J].山西中医学院学报,2018,19(4):24-26,29.
[33] 张靖,胡骞,谭亲友,等.甘草提取物对雷公藤甲素损伤后人肝L-02细胞中UGT1A、MRP2表达的影响[J].中国药房,2018,29(1):65-68.
[34] 姚云洁,肖朗,杨才兴,等.中草药所致DILI患者临床和肝组织病理学特点分析[J].实用肝脏病杂志,2016,19(4):441-444.
[35] 马进,陈岷.鸦胆子油乳注射液不良反应38例回顾性分析[J].中国中医药信息杂志,2014,21(4):116-117.
[36] 梁晶.鸦胆子油乳致肝损害9例临床分析[J].安徽医药,2007(1):93-94.
[37] 王艳辉,赵海平,王伽伯,等.基于“有故无殒”思想的熟大黄对肝脏量-毒/效关系研究[J].中国中药杂志,2014,39(15):2918-2923.
[38] 陈颖,王茉,景莉君,等.基于斑马鱼模型筛选壮骨关节丸毒性药味高效筛选[J].世界科学技术—中医药现代化,2017,19(1):133-141.
[39] 邓培媛,蔡皓东,程经华,等.壮骨关节丸致肝损害30例报告[J].中国新药杂志,1996(3):212-214.
[40] 宋晓静.壮骨关节丸致肝损害一例[J].中外医疗,2009,28(18):181.
[41] 唐进法,王晓艳,温强,等.免疫应激介导的壮骨关节丸致特异质肝损伤评价[J].药学学报,2017,52(7):1033-1040.
[42] 唐进法,王晓艳,杨伟,等.基于统计建模的壮骨关节丸诱发特异质肝损伤相关易感性细胞因子分析[J].药学学报,2018,53(4):574-584.
[43] 赵敏,孙瑞芳,黄坤.骨康胶囊致药物性肝炎1例[J].中国药物警戒,2016,13(1):55-56.
[44] 朱兰,逄瑜,杨乐,等.骨康胶囊肝损伤风险特点及因素分析[J].中国药物警戒,2018,15(4):248-250,256.
[45] 唐鸿珊,常立非.复方青黛丸引起肝损害2例[J].皮肤病与性病,1995(3):73-74.
[46] 倪晓珺,程能能.痔血胶囊组方对原代培养大鼠肝细胞和小鼠肝脏的毒性[J].中国临床药学杂志,2010,19(5):271-275.
[47] 李品,王琦,彭莉,等.痔血胶囊水提物和醇提物对大鼠肝毒性的影响[J].中国实验方剂学杂志,2017,23(8):154-159.
[48] 王晓今,陈成伟,傅青春,等.痔血胶囊单药致群发性肝损伤——附30例分析[J].肝脏,2009,14(4):287-290.
[49] 黄晨,朱光辉,王增寿,等.痔血胶囊致肝损害1例[J].中国临床药学杂志,2009,18(3):173-174.
[50] 张秋玲,杨佳,卢奕霞.白蚀丸致肝损害[J].药物不良反应杂志,2010,12(4):297-298.
[51] 魏戌,谢雁鸣.国内外不良反应因果判断原则及评价方法解读[J].中国中药杂志,2012,37(18):2744-2747.
[52] DANAN G,BENICHOU C.Causality assessment of adverse reactions to drugs--I.A novel method based on the conclusions of international consensus meetings:application to drug-induced liver injuries[J].J Clin Epidemiol,1993,46(11):1323-1330.
[53] ROCKEY D C,SEEFF L B,ROCHON J,et al.Causality Assessment in Drug-Induced Liver Injury Using a Structured Expert Opinion Process:Comparison to the Roussel-Uclaf Causality Assessment Method[J].Hepatology,2010,51(6):2117-2126.
[54] 王伽伯,张乐,郭玉明,等.中药药源性肝损伤因果关系的评价策略和方法[J].药学学报,2018,53(6):920-928.
[55] 肖小河,李秀惠,朱云,等.中草药相关肝损伤临床诊疗指南[J].临床肝胆病杂志,2016,32(5):835-843.
[56] NAVARRO V J,LUCENA M I.Hepatotoxicity induced by herbal and dietary supplements[J].Semin Liver Dis,2014,34:172-193.
[57] TESCHKE R,FRENZEL C,GLASS X,et al.Herbal hepatotoxicity:a critical review[J].Br J Clin Pharmacol,2013,75:630-636.
[58] 王秀坤,赵雍,梁爱华,等.不同产地千里光急性毒性实验研究[J].药物不良反应杂志,2008(2):81-85.
[59] 涂灿,蒋冰倩,赵艳玲,等.何首乌炮制前后对大鼠肝脏的损伤比较及敏感指标筛选[J].中国中药杂志,2015,40(4):654-660.
[60] 李春雨,何琴,唐进法,等.免疫应激介导的何首乌“九蒸九晒”炮制减毒作用及代谢组学研究[J].药学学报,2017,52(7):1069-1076.
[61] 王伽伯,马永刚,金城,等.对应分析在大黄炮制减毒“量-毒”规律研究中的应用[J].中国中药杂志,2009,34(19):2498-2502.
[62] 葛斐林,牛明,韩紫欣,等.白鲜皮制剂相关肝损伤的药物流行病学特征分析[J/OL].中国中药杂志,2018,https://doi.org/10.19540/j.cnki.cjmm.20181217.001.
[63] HE L,YIN P,MENG Y,et al.Immunological synergistic mechanisms of trans-/cis-stilbene glycosides in Heshouwu-related idiosyncratic liver injury[J].Sci.Bull,2017(11):748-751.
[64] Li C Y,Niu M,Bai Z F,et al.Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb,Polygonum multiflorum[J].Front Med,2017,11(2):253-265.
[65] 杨连梅.中药处方点评分析[J].光明中医,2018,33(14):1993-1995.
[66] 庞晶瑶,李雨萌,柏兆方,等.基于高内涵分析的何首乌对肝窦内皮细胞损伤的配伍减毒研究[J].中国现代中药,2015,17(4):331-334.
[67] 杨倩.柴胡挥发油肝毒性“量-时-毒”关系研究[D].济南:山东中医药大学,2011.
[68] 高素强,胡咏川.中药注射剂的应用现状与上市后再评价[J].中国中药杂志,2007,32(13):1370-1372.
[69] 孙学东.应该重视中西药相互不良作用[J].中药新药与临床药理,1997,8(4):9-10.
[70] 牟萍,兰伯恩,吴孟轩.医院81例严重药品不良反应/不良事件报告分析[J].中国药业,2016,25(12):85-88.
[71] 师建平,郭静.中医辨证论治理论体系的研究现状与发展趋势[J].中华中医药杂志,2013,28(9):2508-2510.
[72] 王伽伯,李春雨,朱云,等.基于整合证据链的中草药肝毒性客观辨识与合理用药:以何首乌为例[J].科学通报,2016,61(9):971-980.