辛热类有毒中药风险-效益阈与效毒机制研究

辛热类有毒中药效毒共存、应用广泛，虽疗痼冷顽疾优势明确，但安全问题突出。其毒、效表征受诸多因素影响，临床如何量化、把控？是亟待解决的困惑。.前期工作发现，辛热药功效、毒性表达有共通联系及量化可能，可为阐释其临床风险-效益提供依据。本次提出假说“辛热类有毒中药的毒与效之间存在可被量化、核心化的‘阈’，是临床风险-效益评价的关键环节，也是效毒机制阐释的前提，可为中药毒性研究提供新认知”。选择辛热类有毒代表性药物仙茅、蛇床子、川乌、草乌、附子及雪上一枝蒿，综合采用数据信息挖掘、多准则决策、计算机模拟、病生理学及分子生物学等方法，挖掘辛热类有毒中药风险-效益多维“阈”，筛选其核心的风险-效益阈并量化，在“阈”前提下开展针对性的效毒机制研究，并以同类辛热有毒药进行“阈”验证。.本研究从新视角认知辛热类有毒中药的风险-效益，为有毒中药研究提供示范，为临床安全用药提供直接、客观的依据。

Chinese herbs with acrid, hot and toxic properties, which have been widely used and proven to have both toxicity and curative effects, are known for their advantages in the treatment of obstinate cold syndrome, but can cause severe safety problems. The toxicity-efficiency characteristics of these herbs are affected by many factors. Therefore, the question of how to measure and control these factors in clinical demands our urgent attention. .Previous studies have revealed the common connections and possibility of quantification between toxicity and efficacy of Chinese herbs with acrid, hot and toxic properties, which would be helpful to elucidate the clinical risks and benefits. This study proposes that there is Yu existing between toxicity and efficacy of Chinese herbs with acrid, hot and toxic properties, which can be quantified and put at the core of the problem. It is the key to estimate risk-benefit clinically and is the precondition to elucidate the mechanisms of efficacy and toxicity. The hypothesis will provide a new perspective for future toxicity studies of Chinese herbs. In this research, Rhizoma Curculiginis, Fructus Cnidii, Radix Aconiti，Radix Aconiti Kusnezoffii，Radix Aconiti Lateralis Praeparata and Radix Aconiti Brachypodi were used as sample drugs，combined with data mining, multi-criteria decision analysis, computer simulation, pathophysiology, molecular biology and other methods to excavate multidimensional Yu of risk-benefit of Chinese herbs with acrid, hot and toxic properties, to screen core conditions of Yu and quantify them. Then, research on the mechanisms of efficacy and toxicity, including targets and signal pathways, will be conducted on the premise of Yu. Finally, sample Chinese herb with same properties would be introduced to verify the results concerning Yu. This study provides a new understanding of the risk and benefit of Chinese herbs with acrid, hot and toxic properties from another perspective, offers a demonstration for studies of Chinese herbs with toxic properties, and provide direct and objective basis for clinical safe use of Chinese herbs.