中药的心脏效-毒双向作用机制探析与用药警戒思考

Mechanism analysis and pharmacovigilance considerations of traditional Chinese medicine with"potency-toxicity"bi-directional effect of heart

目的针对具有心脏治疗作用又可能引发心脏损伤的“效-毒双向作用”中药进行机制探析并提出用药警戒思考。方法检索中国知网、万方数据、维普网等数据库,检索时间为建库起至2021年11月30日。系统挖掘具有心脏效-毒双向作用的药物,结合文献学、生物信息技术手段,分析其效-毒双向作用成分、机制及“效-毒”转化因素。结果山豆根、吴茱萸、麦冬、两面针、香加皮等10味中药具有心脏效-毒双向作用,其作用成分类型包括生物碱类、强心苷类、皂苷类等,作用机制主要与AKT/AMPK/mTOR通路及心肌Ca^(2+)-Na^(+)-K^(+)通道有关。效-毒转化与机体原患心脏疾病、体质差异,用药剂量、用法、配伍,以及药物效-毒成分等多方面因素有关。结论心脏效-毒双向作用中药的用药需要多重措施警戒,防止该类中药由效转毒,特别要加强原患心脏疾病患者的用药监护。

Objective To investigate the mechanism and provide suggestions for the pharmacovigilance and rational use of traditional Chinese medicine with cardiac therapeutic effect and possible cardiac injury.Methods Traditional Chinese medicines with"potency-toxicity:bi-directional effect of the heart was Systematically search and excavatd from Chinese periodical literature databases such as CNKI,Weipu,Wanfang Data Knowledage Service Platform.The retrieval time was from inception to November 30,2021.Analyze the components,mechanisms,transformation factors of"potencytoxicity"effect of these medicines by combining bibliometric and bioinformatics tools.Results 10 Chinese herbs,such as Shandougen(Sophorae Tonkinensis Radix Et Rhizoma),Wuzhuyu(Euodiae Fructus),Maidong(Ophiopogonis Radix),Liangmianzhen(Zanthoxyli Radix)and Xiangjiapi(Periplocae Cortex),had cardiac"potency-toxicity"bi-directional effect.The types of bi-directional components include alkaloids,cardiac glycosides,saponins,etc.The mechanism of bi-directional effects is mainly related to the AKT/AMPK/mTOR pathway and myocardial Ca^(2+)-Na^(+)-K^(+) channels.The potency-toxicity effect conversion is related to the patient’s pre-existing heart disease,physical differences,drug dosage,administration and combination,as well as potency-toxicity components and other factors.Conclusion The administration of cardiac potency-toxicity bi-directional effect traditional Chinese medicines requires multiple measures of pharmacovigilance to prevent the conversion of such medicines from potency to toxicity,especially to enhance the attention to the medication monitoring of patients with pre-existing cardiac diseases.