[關(guān)鍵詞]
[摘要]
中醫(yī)藥在疾病的治療與預(yù)防方面有數(shù)千年歷史,為中華民族繁衍生息作出突出貢獻(xiàn),中藥的安全性問題卻面臨重大質(zhì)疑。心臟毒性對(duì)于中藥臨床毒副作用研究以及創(chuàng)新藥物研發(fā)至關(guān)重要,目前關(guān)于心臟毒性的相關(guān)研究日益增多,大部分研究主要集中在中藥減輕腫瘤化療后所誘導(dǎo)心臟毒性和其他藥物所致心臟不良反應(yīng),中藥自身所發(fā)生的心臟毒性機(jī)制及安全用藥方面研究相對(duì)匱乏。心臟電生理現(xiàn)象作為心臟細(xì)胞的基本生命活動(dòng)特性之一,心肌細(xì)胞正常的電生理活動(dòng)保障心臟功能的有效運(yùn)轉(zhuǎn)。為了深入研究中藥自身成分中的心臟毒性與作用機(jī)制,提高中藥臨床應(yīng)用的安全性,基于鉀離子通道、鈉離子通道、鈣離子通道的心臟電生理特性,總結(jié)中藥單體與復(fù)方誘導(dǎo)心臟毒性的機(jī)理機(jī)制。同時(shí)借助計(jì)算機(jī)虛擬模型、人誘導(dǎo)多能干細(xì)胞分化的心肌細(xì)胞(hiPSC-CMs)和心臟類器官(hCO)、膜片鉗技術(shù)等國際公認(rèn)的藥物心臟毒性評(píng)價(jià)技術(shù)創(chuàng)建中藥心臟毒性安全評(píng)價(jià)平臺(tái),運(yùn)用中醫(yī)傳統(tǒng)理論為中藥在臨床應(yīng)用時(shí)所誘導(dǎo)心臟毒性提供相應(yīng)的預(yù)防措施,為鑒定中藥心臟毒性以及中藥臨床應(yīng)用所致心臟不良反應(yīng)提供科學(xué)依據(jù),為中藥新藥研發(fā)開辟新的研究方向。
[Key word]
[Abstract]
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.
[中圖分類號(hào)]
R992
[基金項(xiàng)目]
國家自然科學(xué)基金重點(diǎn)項(xiàng)目(82030120);國家自然科學(xué)基金青年基金項(xiàng)目(81503435);國家自然科學(xué)基金項(xiàng)目(82074226);河南省中管局國家中醫(yī)臨床研究基地科研專項(xiàng)(2018JDZX058);河南省高等學(xué)校重點(diǎn)科研項(xiàng)目計(jì)劃(21A360011);河南省中醫(yī)藥科學(xué)研究專項(xiàng)課題(2022ZY2009);河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃聯(lián)合共建項(xiàng)目(LHGJ20200090);河南省重點(diǎn)研發(fā)與推廣專項(xiàng)(科技攻關(guān))項(xiàng)目(212102310759,212102311079,242102310554,222301420086);橫向課題(XZ2022013);華通國康醫(yī)學(xué)科研專項(xiàng)(2023HT034)