基于基因算法辅助人工神经网络的吴茱萸“甘补药制”炮制减毒机制研究

Reducing poison by processing is a characteristic of Traditional Chinese Medicine (TCM) theory and drug treatment, and plays an important role in safety of drug. The scientific connotation of reducing poison by processing is one of the important contents of the modern research of TCM. Euodiae Fructus is a traditional paregoric, its characteristic is hot. Euodiae Fructus has slight toxic so that its processed product is widely used by orally in clinic. Its product processed by licorice is the only one contained by Chinese pharmacopoeia, which is consistent with the record of literature. In historical document, "Gan Tonics Processing" can reduce the poison of Euodiae Fructus and tonifying Qi. However, the research on the correlation between the processing by licorice of Euodiae Fructus and the theory of "Gan Tonics Processing" has not been reported. In this study, enhanced fingerprints will be established to obtain the "quality" and "quantity" double chemical information of raw materials and processed products. Then, hepatotoxicity information of each stage of processing samples will be got by high intension cell imaging. Finally, the key points of chemical-toxicity difference information will be acquired based on genetic algorithm aided Artificial Neural Networks. On the above research foundation, a research method on the mechanism of reducing poison by Euodiae Fructus "Gan Tonics Processing" based on genetic algorithm aided Artificial Neural Networks will be established. This study will explain the theory of "Gan Tonics Processing" application in processed Euodiae Fructus, and provide a new research idea and method in the processing theory of TCM.

炮制减毒是中医药特有传统理论及药物处理方法，是中药安全用药的重要保障。阐述中药炮制减毒的科学内涵是中药现代化研究的重要内容之一。中药吴茱萸为传统止痛良药，其性热，有小毒，口服入药则多为制品。目前甘草制吴茱萸为《中国药典》中唯一收载的吴茱萸炮制品种，这与文献记载“甘补药制”可解吴茱萸毒，甘缓益气相吻合，但吴茱萸甘草炮制与传统“甘补药制”的相关性尚缺乏研究。本课题拟首先采用增强型指纹图谱技术获取吴茱萸生品及炮制品的“质”、“量”双重化学信息；采用高内涵细胞影像技术获取炮制各阶段样品肝毒性效应信息；进而采用基因算法辅助人工神经网络获取吴茱萸甘草炮制“化学-毒性”差异信息关键点，预期建立一种基于基因算法辅助人工神经网络的吴茱萸“甘补药制”炮制减毒机制研究方法，阐述“甘补药制”这一炮制理论在吴茱萸甘草炮制中的应用特点，为中药炮制理论研究提供新的研究思路与方法。

本研究以传统中药吴茱萸为模型药物，首先从醇提成分、水提成分及挥发性成分层次采用指纹图谱结合化学计量学的方法对吴茱萸生品及不同炮制品进行含量测定及规格、基原的区分；进一步对吴茱萸生品及炮制品中的各种活性成分进行生物药剂学特征的体外快速评价；进而对吴茱萸炮制前后抗炎镇痛活性及肝脏代谢酶活性进行测定；随后采用血清药化实验及网络药理学预测手段对吴茱萸发挥抗炎镇痛作用的分子作用机制进行研究；进而基于关联分析研究吴茱萸与甘味中药的配伍规律，研究甘草及甘草组分与吴茱萸配伍发挥减毒作用的物质基础；然后基于吴茱萸挥发性成分及非挥发性成分对吴茱萸“陈久者良”理论的物质基础进行探究，并借助网络药理学对该分子作用机制进行了研究。本课题立足于现代有毒中药炮制的关键问题，以中药传统理论为基础，将中药学、中医基础理论、中药化学、生物药剂学、物理化学、化学计量学等多学科有机结合，建立了一种基于化学计量学与生物药剂学的吴茱萸炮制作用规律研究，为有毒中药炮制减毒理论的研究提供新的技术思路和实用方法。