附子双酯型二萜生物碱对代谢酶的影响及心肌毒性研究进展

The research progress on effects of diester-diterpenoid alkaloidson metabolic enzymes and myocardial toxicity of Fuzi

关键词:  附子  双酯型二萜生物碱  心肌毒性  CYP450酶  配伍

Key words:  Fuzi  diester diterpenoid alkaloids  myocardial toxicity  cytochromes P450  compatibility

摘要:

附子是一种常用的中草药，具有广泛的药理作用，但心脏毒性显著。其主要毒性成分为双酯型二萜生物碱，如：乌头碱、中乌头碱、次乌头碱，如何减轻附子毒性但又不影响药效格外重要。多年来，众多学者不断深入研究附子生物碱的毒性机制，并取得了一定的共识。文章通过总结国内外研究资料，阐述了附子所含有的双酯型二萜生物碱对细胞色素P450酶系的影响，以及与其心脏毒性相关心肌的氧化损伤、细胞凋亡、缝隙连接蛋白Cx43和钠、钾、钙离子稳态的影响，并阐述了与上述机制相关的甘草、人参与附子配伍的作用机制。

Abstract:

Fuzi is a commonly used Chinese herbal medicine with a wide range of pharmacological effects, but the cardiotoxicity was significant. Its main toxic components are diester diterpenoid alkaloids, such as aconitine, hypaconitine and mesaconitine. How to reduce Fuzi toxicity without affecting drug efficacy is particularly important. Over the years, many scholars have been studying in depth the toxicity mechanism of alkaloids in Fuzi and achieved a certain degree of consensus. By summarizing domestic and foreign research data, this article describes the effects of diester-diterpenoid alkaloids contained in Fuzi on cytochrome P450 enzymes, as well as the oxidative damage, apoptosis, gap junction protein Cx43, and Na⁺, K⁺,Ca²⁺ homeostasis of the myocardium associated with its cardiotoxicity. The mechanism of compatibility of Fuzi-Gancao, Fuzi-Renshen associated with the above mechanisms are described.