附子心脏毒效的多维评价和整合分析研究进展

摘要

As a famous geo-authentic medicine distributed in Sichuan Province,Radix Aconiti Lateralis Praeparata is also a traditionally toxic medicine with curative effect in clinic.Heart is the key target for both toxicity and efficacy of Radix Aconiti Lateralis Praeparata.However,the correlation between toxicity and efficacy on heart remains unknown.Under the guidance of the research idea "multidimensional evaluation and integrated analysis between ‘ toxicity and efficacy’ for Chinese materia medica" proposed by professor Peng Cheng,the article tightly focused on the six factors as "variety,quality,processing,property,efficacy,application" of Chinese materia medica.The research status of ‘ toxicity-efficacy’ material basis,mechanism,and effect-enhancing and toxicity-reducing principle for Radix Aconiti Lateralis Praeparata on heart were summarized based on our years of researches and other relative researches at home and abroad.Cardiac toxicity-efficacy mechanism was integrated analyzed then.It was shown that diester-type alkaloids (DA) was material base for heart toxicity in Radix Aconiti Lateralis Praeparata,while total alkaloids (AD),water-soluble alkaloids (WA),polysaccharide and some other compounds in Radix Aconiti Lateralis Praeparata were responsible for effects of cardiotonic and protecting myocardial cells.There were the same targets in myocardial cells for toxicity and efficacy of Radix Aconiti Lateralis Praeparata,such as cell morphology and function,membrane stability,cellular environmental homeostasis,ion transport-related ATPase and channels,and energy metabolism.However,there was some respective mechanism for each other.Multi-means could be taken to control cardiac toxicity and enhance effects on heart for Radix Aconiti Lateralis Praeparata,including legal processing,reasonable compatibility,differentiation for use,extending time of decoction,dosage control.%附子是著名的川产道地药材,也是传统确有疗效有毒中药,心脏是其重要毒效靶器官,但毒-效相关性不甚明确.本文在彭成教授提出的“中药‘毒与效’的多维评价与整合分析”的研究思路指导下,紧密围绕中药“品质制性效用”六大元素,以本团队多年的研究成果为基础,并广泛整理国内外相关研究成果,按附子的心脏“毒-效”物质基础-附子的心脏“毒-效”机制-附子对心脏的增效减毒原理3个层面综述研究现状,整合分析附子对心脏的毒效机制.结果显示,附子中所含的双酯型生物碱是附子致心脏毒性的主要物质基础,而附子的强心和保护心肌作用是附子总碱、附子水溶性生物碱、附子多糖及其他一些成分等多成分综合作用的结果;附子对心脏的毒机制和效机制在心肌细胞上存在相同靶点,主要包括细胞形态和功能、细胞膜稳定性、细胞内环境稳态、离子转运相关ATP酶和通道、细胞能量代谢;但又有各自的独有机制;可通过依法炮制、合理配伍、辨证用药、延长煎煮时间和控制剂量等多种手段控制附子的心脏毒性和发挥其强心、保护心肌作用.