He Jian, Wu Ping, Dong Yu, Gao Rui
Office of Drug Clinical Trial Institution,Guang'anmen Hospital,China Academy of Chinese Medical Sciences Beijing 100053,China.
Institute of Clinical Pharmacology,Xiyuan Hospital,China Academy of Chinese Medical Sciences Beijing 100091,China.
Zhongguo Zhong Yao Za Zhi. 2019 Mar;44(5):1010-1018. doi: 10.19540/j.cnki.cjcmm.20181205.003.
The aim of this paper was to provide reference for the clinical safety use of aconite through the retrieval of literature about adverse reactions,predict its mechanism of cardiac toxicity by using network pharmacology,and provide ideas for the studies on toxicity mechanism of toxic Chinese medicines. The papers on adverse reactions of aconite were searched to established a database and summarize the adverse reactions of aconite. The results of literature review showed that the main causes for adverse reactions in clinical use of aconite included overdose use,short cooking time,consumption of medicinal liquor/medicinal diet,external use and misuse and so on. Therefore,the dosage of aconite should be strictly followed in clinical application,and the decoction method should be notified to the patients in detail to avoid taking the medicinal liquor and diet containing aconite,so as to prevent the occurrence of adverse reactions as much as possible,and make the best use of aconite in clinical application in avoid its toxicity. At the same time,based on the results of literature review,the network construction and visual analysis of cardio toxicity produced by aconite were carried out by using the network pharmacology technologies. RESULTS: showed that aconite can be applied to eight biological processes such as action potential of cardiac myocytes,cardiac conduction-related cell signal transduction,cardiac myocytes contraction,action potential involved in cardiac myocytes contraction,and signal transduction from atrial myocardial cells to atrioventricular node cells,and three target genes(SCN5 A,GJA1,GJA5). It was predicted that Aconiti Lateralis Radix Praeparata may influence cardiomyocyte depolarization,intercellular information transmission and material exchange by acting on three target genes(SCN5 A,GJA1,GJA5) and regulating the sodium channel protein and the expression of gap junction protein,thus affecting the heart rhythm as well as its structure and function and causing cardiac toxicity.
本文旨在通过检索附子不良反应的文献,为附子临床安全用药提供参考,运用网络药理学预测其心脏毒性机制,为有毒中药毒性机制研究提供思路。检索有关附子不良反应的文献并建立数据库,总结附子的不良反应。文献综述结果表明,附子临床应用中不良反应的主要原因包括过量使用、煎煮时间短、服用药酒/药膳、外用及误用等。因此,临床应用附子时应严格遵循剂量规定,并详细告知患者煎煮方法,避免服用含附子的药酒和药膳,以尽可能预防不良反应的发生,在避免其毒性的同时充分发挥附子在临床应用中的作用。同时,基于文献综述结果,运用网络药理学技术对附子产生的心脏毒性进行网络构建和可视化分析。结果显示,附子可作用于心肌细胞动作电位、心脏传导相关细胞信号转导、心肌细胞收缩、参与心肌细胞收缩的动作电位以及心房肌细胞至房室结细胞的信号转导等八个生物学过程,并涉及三个靶基因(SCN5A、GJA1、GJA5)。预测制附子可能通过作用于三个靶基因(SCN5A、GJA1、GJA5),调节钠通道蛋白和缝隙连接蛋白的表达,影响心肌细胞去极化、细胞间信息传递和物质交换,进而影响心脏节律及其结构和功能,导致心脏毒性。