摘要
中医药在疾病的治疗与预防方面有数千年历史,为中华民族繁衍生息作出突出贡献,中药的安全性问题却面临重大质疑。心脏毒性对于中药临床毒副作用研究以及创新药物研发至关重要,目前关于心脏毒性的相关研究日益增多,大部分研究主要集中在中药减轻肿瘤化疗后所诱导心脏毒性和其他药物所致心脏不良反应,中药自身所发生的心脏毒性机制及安全用药方面研究相对匮乏。心脏电生理现象作为心脏细胞的基本生命活动特性之一,心肌细胞正常的电生理活动保障心脏功能的有效运转。为了深入研究中药自身成分中的心脏毒性与作用机制,提高中药临床应用的安全性,基于钾离子通道、钠离子通道、钙离子通道的心脏电生理特性,总结中药单体与复方诱导心脏毒性的机理机制。同时借助计算机虚拟模型、人诱导多能干细胞分化的心肌细胞(hiPSC-CMs)和心脏类器官(hCO)、膜片钳技术等国际公认的药物心脏毒性评价技术创建中药心脏毒性安全评价平台,运用中医传统理论为中药在临床应用时所诱导心脏毒性提供相应的预防措施,为鉴定中药心脏毒性以及中药临床应用所致心脏不良反应提供科学依据,为中药新药研发开辟新的研究方向。
Chinese medicine has a history of thousands of years in the treatment and prevention of diseases and has made outstanding contributions to the prosperity of the Chinese nation,while the safety of Chinese medicine has faced major questions.Cardiotoxicity is crucial to the study of clinical toxicity and innovative drug development of Chinese medicine.Currently,there is an increasing number of cardiotoxicity studies,but most of them focus on the mitigation of cardiotoxicity induced by tumor chemotherapy and the treatment of cardiac adverse reactions caused by other drugs,while the cardiotoxicity mechanism of Chinese medicine and the safe use of Chinese medicine have been studied relatively little.Cardiac electrophysiological phenomena,as one of the fundamental life activity characteristics of cardiac cells,ensure the effective functioning of the heart through the normal electrophysiological activities of cardiomyocytes.In order to study the cardiotoxicity and mechanism of action of the components of traditional Chinese medicines and to improve the safety of clinical application of traditional Chinese medicines,this paper summarizes the mechanism of cardiotoxicity induced by traditional Chinese medicines in monomers and combinations based on the cardiac electrophysiological properties of potassium ion channels,sodium ion channels and calcium ion channels.At the same time,with the help of computer virtual model,human induced pluripotent stem cell differentiated cardiomyocytes(hiPSC-CMs)and heart-like organ(hCO),membrane clamp technology and other internationally recognized drug cardiotoxicity evaluation techniques,we created a platform for the safe evaluation of cardiotoxicity of Chinese medicine,and provided corresponding preventive measures for the cardiotoxicity induced by traditional Chinese medicine theories in the clinical application of Chinese medicine,so as to help to identify the cardiotoxicity and the adverse cardiac effects caused by the clinical application of Chinese medicine.It will provide scientific basis for the identification of cardiotoxicity and adverse cardiac reactions caused by clinical application of traditional Chinese medicine,and open up a new research direction for the research and development of new traditional Chinese medicine.
作者
王选阳
高原
李彬
于瑞
谢世阳
周璐烨
孙雨蝶
朱明军
WANG Xuanyang;GAO Yuan;LI Bin;YU Rui;XIE Shiyang;ZHOU Luye;SUN Yudie;ZHU Mingjun(Heart Center,The First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,China;The First Clinical Medical College of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,China;Henan Engineering Research Center of Chinese Medicine Safety Evaluation and Risk Prevention and Control,The First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,China)
出处
《药物评价研究》
北大核心
2025年第1期256-268,共13页
Drug Evaluation Research
基金
国家自然科学基金重点项目(82030120)
国家自然科学基金青年基金项目(81503435)
国家自然科学基金项目(82074226)
河南省中管局国家中医临床研究基地科研专项(2018JDZX058)
河南省高等学校重点科研项目计划(21A360011)
河南省中医药科学研究专项课题(2022ZY2009)
河南省医学科技攻关计划联合共建项目(LHGJ20200090)
河南省重点研发与推广专项(科技攻关)项目(212102310759,212102311079,242102310554,222301420086)
横向课题(XZ2022013)
华通国康医学科研专项(2023HT034)。
关键词
中药
心脏毒性
电生理
离子通道
安全性评价
预防措施
traditional Chinese medicines
cardiotoxicity
electrophysiology
ion channel
safety assessment
preventive measures
