基于关联网络挖掘的中药不良反应与药性相关关系分析及用药警戒探讨
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摘要
目的:解析中药不良反应的发生与其性味归经、有毒无毒等药性之间的相关关系,从中药药性分布探讨中药用药警戒。方法:筛选《中华人民共和国药典》2015版第一部中药饮片,通过系统文献检索分析每种中药饮片不良反应报道,采取频数分布及关联规则挖掘、网络构建方法,分析与中药临床用药警戒相关的药性参数。结果:618种中药及饮片中有152种中药有不良反应报道,其中无毒中药109种,占71.71%。大毒及有毒中药发生不良反应的比例明显高于无毒中药,分别达到70%和66.67%。温性和寒性中药发生不良反应的频数最高,而热性中药发生不良反应的比例最高;苦味和辛味发生不良反应的中药种数最多;归肝、肺、肾等经发生不良反应的中药种数最多。关联规则挖掘及关联网络结果显示,包含大毒、有毒、温、热以及苦味、辛味和归心、肝等经的关联规则最多,大毒与归肝经组合发生不良反应的概率高达86%;而温热性中药与辛苦味的组合可以导致不良反应发生概率达80%以上,与肝经的组合可以达到75%。结论:中药不良反应的发生除了与毒性记载密切相关之外,也与中药的性味归经等存在一定的关联关系,这些结果可以为中药尤其是无毒性记载中药的用药安全和警戒提供参考。
Objective: To analyze the correlation between adverse drug reactions(ADRs) of Traditional Chinese Medicine(TCM) and its properties, such as meridian tropism, toxicity and non-toxicity, and to explore the pharmacovigilance of TCM from the distribution of its properties. Methods: Chinese medicine and its decoction pieces were screened from Pharmacopoeia of People's Republic of China(1 st section, 2015 edition), and the ADRs of each Chinese Medicins(CMs)were analyzed by systematic literature searching. The properties parameters related to ADRs of CMs were screened by frequency distribution, association rule mining and network construction methods. Results: Among 618 kinds of CMs,152 kinds of CMs had been reported to have adverse reactions. A total of 109 kinds of non-toxic CMs accounted for71.71%. The incidence of adverse reactions of"strong toxic"and toxic CMs was significantly higher than that of nontoxic CMs, reaching 70% and 66.67% respectively. For the distribution of cold and hot nature, the frequency of adverse reactions of warm and cold herbs is the highest, while the proportion of adverse reactions of hot herbs is the highest; for the distribution of taste, bitter and acrid herbs have the largest number of adverse reactions; for the distribution of meridians tropism, liver, lung, kidney present the largest number of ADRs. Results of association rule mining and association network showed that the association rules including"strong toxic", toxic, warm, hot, bitter, acrid and heart,liver and other meridians are the most, and the combination of"strong toxic"and liver meridians has a high confidence equal to 86%; CMs with the combination of warm and bitter can lead to confidence of more than 80%. Moreover, the confidence of combination of warm and liver meridian can reach 75%. Conclusion: The occurrence of ADRs of TCMs is not only closely related to toxicity records, but also related with the cold-hot nature, taste and meridian tropism of TCM.These results can provide reference for the safety use and pharmacovigilance of TCM, especially TCMs with non-toxic records.
Objective: To analyze the correlation between adverse drug reactions(ADRs) of Traditional Chinese Medicine(TCM) and its properties, such as meridian tropism, toxicity and non-toxicity, and to explore the pharmacovigilance of TCM from the distribution of its properties. Methods: Chinese medicine and its decoction pieces were screened from Pharmacopoeia of People's Republic of China(1 st section, 2015 edition), and the ADRs of each Chinese Medicins(CMs)were analyzed by systematic literature searching. The properties parameters related to ADRs of CMs were screened by frequency distribution, association rule mining and network construction methods. Results: Among 618 kinds of CMs,152 kinds of CMs had been reported to have adverse reactions. A total of 109 kinds of non-toxic CMs accounted for71.71%. The incidence of adverse reactions of"strong toxic"and toxic CMs was significantly higher than that of nontoxic CMs, reaching 70% and 66.67% respectively. For the distribution of cold and hot nature, the frequency of adverse reactions of warm and cold herbs is the highest, while the proportion of adverse reactions of hot herbs is the highest; for the distribution of taste, bitter and acrid herbs have the largest number of adverse reactions; for the distribution of meridians tropism, liver, lung, kidney present the largest number of ADRs. Results of association rule mining and association network showed that the association rules including"strong toxic", toxic, warm, hot, bitter, acrid and heart,liver and other meridians are the most, and the combination of"strong toxic"and liver meridians has a high confidence equal to 86%; CMs with the combination of warm and bitter can lead to confidence of more than 80%. Moreover, the confidence of combination of warm and liver meridian can reach 75%. Conclusion: The occurrence of ADRs of TCMs is not only closely related to toxicity records, but also related with the cold-hot nature, taste and meridian tropism of TCM.These results can provide reference for the safety use and pharmacovigilance of TCM, especially TCMs with non-toxic records.
引文
1王莹莹,杨金生.中医药发展的几个关键问题.中国中医药信息杂志, 2013, 20(2):6-7+23.
2 张丹参,于肯明,王建刚.药理学.北京:人民卫生出版社, 1981:2831
3 李彦奇,曹俊岭.中药药性理论与临床疗效的关系.中华中医药学会2013年药房管理分会学术年会论文汇编, 2013.
4 周珂,谭勇,刘忠第,等.中药寒热药性及其毒副作用研究现状.中国中医药信息杂志, 2015, 22(4):129-132.
5 赵益,左铮云,刘霞,等.中药不良反应与其药性相互关系的文献研究?.中草药, 2011, 42(2):392-397.
6 廖建萍,欧阳荣,刘红宇,等. 90种中药不良反应与其药性相互关系研究.中医药导报, 2014, 20(11):16-19.
7 中华人民共和国药典委员会.中华人民共和国药典2015版(一部).北京:中国医药出版社, 2015.
8 钟莹.药物不良反应因果关系评价方法的对比.广州:广州中医药大学硕士研究生学位论文, 2015.
9 Team R D C. A language and environment for statistical computing.Computing, 2013, 1:12-21.
10 Hahsler M, Gruen B, Hornik K, et al. The arules package. Methods,2006, 15(1):1-14.
11 Hahsler M, Chelluboina S. Visualizing association rules:Introduction to the R-extension package arulesViz. R project module, 2011, 1(1):223-238.
12 张冰,林志健,张晓朦,等.中药药物警戒思想的挖掘与实践.药物流行病学杂志, 2016, 25(7):405-408.
13 于洪礼,于冬梅,宋海波,等.何首乌及其常用制剂相关不良反应文献研究及风险因素分析.中国药物警戒, 2018, 15(8):470-475.
14 Tan Y, Li J, Liu X, et al. Deciphering the differential toxic responses of Radix aconiti lateralis praeparata in healthy and hydrocortisonepretreated rats based on serum metabolic profiles. Journal of proteome research, 2012, 12(1):513-524.
15 Haller C A, Benowitz N L. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. The New England journal of medicine, 2000, 343(25):1833-1838.
16 蒋一帆,高建超,田春华,等.毒性药材天仙子的文献研究及风险探讨.中国药物警戒, 2016, 13(3):165-168.
17 石红.马钱子中毒致肝损害1例.中国药物滥用防治杂志, 2008, 14(4):244-244.
18 张晓朦,李凡,张冰,等.数据挖掘乌头类中成药不良反应特点与合理用药警戒.中国中药杂志, 2018, 43(2):216-221.
19 肖翾.斑蟊素中毒的毒理学初步研究.重庆:重庆医科大学硕士研究生学位论文, 2017.
20 姚敏,金柳燕,代文月,等.栀子对闹羊花肝毒性的解毒效应的动物实验研究.时珍国医国药, 2011, 22(9):2183-2185.
21 王雨,张冰,林志健,等.平肝息风类中药饮片安全问题分析与用药警戒思考.中华中医药杂志, 2016, 31(11):4643-4648.
22 尹利顺,李晓宇,孙蓉.千里光临床不良反应成因分析.中国药物警戒, 2015, 12(3):160-163.
23 方国祥,师晶丽,陈坤支,等.植物类中草药引起的肾损害.中国临床医生, 2006(12):10-16.
24 周小丽.中药发生不良反应的原因及解决对策分析.中国处方药,2017, 15(4):47-48.
2 张丹参,于肯明,王建刚.药理学.北京:人民卫生出版社, 1981:2831
3 李彦奇,曹俊岭.中药药性理论与临床疗效的关系.中华中医药学会2013年药房管理分会学术年会论文汇编, 2013.
4 周珂,谭勇,刘忠第,等.中药寒热药性及其毒副作用研究现状.中国中医药信息杂志, 2015, 22(4):129-132.
5 赵益,左铮云,刘霞,等.中药不良反应与其药性相互关系的文献研究?.中草药, 2011, 42(2):392-397.
6 廖建萍,欧阳荣,刘红宇,等. 90种中药不良反应与其药性相互关系研究.中医药导报, 2014, 20(11):16-19.
7 中华人民共和国药典委员会.中华人民共和国药典2015版(一部).北京:中国医药出版社, 2015.
8 钟莹.药物不良反应因果关系评价方法的对比.广州:广州中医药大学硕士研究生学位论文, 2015.
9 Team R D C. A language and environment for statistical computing.Computing, 2013, 1:12-21.
10 Hahsler M, Gruen B, Hornik K, et al. The arules package. Methods,2006, 15(1):1-14.
11 Hahsler M, Chelluboina S. Visualizing association rules:Introduction to the R-extension package arulesViz. R project module, 2011, 1(1):223-238.
12 张冰,林志健,张晓朦,等.中药药物警戒思想的挖掘与实践.药物流行病学杂志, 2016, 25(7):405-408.
13 于洪礼,于冬梅,宋海波,等.何首乌及其常用制剂相关不良反应文献研究及风险因素分析.中国药物警戒, 2018, 15(8):470-475.
14 Tan Y, Li J, Liu X, et al. Deciphering the differential toxic responses of Radix aconiti lateralis praeparata in healthy and hydrocortisonepretreated rats based on serum metabolic profiles. Journal of proteome research, 2012, 12(1):513-524.
15 Haller C A, Benowitz N L. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. The New England journal of medicine, 2000, 343(25):1833-1838.
16 蒋一帆,高建超,田春华,等.毒性药材天仙子的文献研究及风险探讨.中国药物警戒, 2016, 13(3):165-168.
17 石红.马钱子中毒致肝损害1例.中国药物滥用防治杂志, 2008, 14(4):244-244.
18 张晓朦,李凡,张冰,等.数据挖掘乌头类中成药不良反应特点与合理用药警戒.中国中药杂志, 2018, 43(2):216-221.
19 肖翾.斑蟊素中毒的毒理学初步研究.重庆:重庆医科大学硕士研究生学位论文, 2017.
20 姚敏,金柳燕,代文月,等.栀子对闹羊花肝毒性的解毒效应的动物实验研究.时珍国医国药, 2011, 22(9):2183-2185.
21 王雨,张冰,林志健,等.平肝息风类中药饮片安全问题分析与用药警戒思考.中华中医药杂志, 2016, 31(11):4643-4648.
22 尹利顺,李晓宇,孙蓉.千里光临床不良反应成因分析.中国药物警戒, 2015, 12(3):160-163.
23 方国祥,师晶丽,陈坤支,等.植物类中草药引起的肾损害.中国临床医生, 2006(12):10-16.
24 周小丽.中药发生不良反应的原因及解决对策分析.中国处方药,2017, 15(4):47-48.