基于体内生物标记物变化规律的栀子大黄汤防治酒疸动物模型的作用机制研究

The preparation of traditional chinese medicine syndrome animal model plays a crucial role to evaluate the therapeutic efficacy of chinese medical herbs. However, wheather the animal model can reflect the properties of traditional chinese medicine syndrome remains unclear..Jaundice associated with elevated bilirubin is a common clinical liver disease symptoms. According to the different pathogenesis and pathological stage Jaundice can be divided into different categories in traditional chinese medicine.Alcohol jaundice is the morbid condition chiefly manifested as icteric sclera,skin presents yellowish color and dark brownish urin.The pathogenesis has been reported that the stomach and spleen can be impaired by too much drinking, obstruction of bile ducts.When dampness-cold accumulates in the middle-jiao,bile circulation is obstructed,and bile overflows to muscle and skin leading to jaundice in the end. Recently，the herbal drugs played an important role in the therapy of liver disorders and alcohol jaundice.ZhiZiDaHuang Tang is a classical traditional chinese medicine (TCM)formula recorded originally in “Synopsis of Golden Chamber” in the period of Han Dynasty of China,which is an aqueous extract from the mixture of four herbal drugs: Zhizi, Dahuang,Zhishi and Douchi used for treating liver disorders and alcohol jaundice,primary biliary cirrhosis,and cholestatic liver disease in clinical. . Based on our previous research, this study is to prepare the animal model which can reflect the properties of alcohol jaundice and its formative background, and to further evaluate the therapeutic efficacy of Zhizidahuang-Tang, a classical medical formular for treating alcohol jaundice on this model.Based upon this, we try to elucidate the biomedical basis of alcohol jaundice's formation and the therapeutic mechanisms of Zhizidahuang-Tang.. Based on TCM theory and therapeutic principle of alcohol jaundice, Chinese medical herbs integrated with chemical liver injury agents was applied to replicated alcohol jaundice animal model. Metabonomics combined with clinical chemistry were used to evaluate alcohol jaundice animal model and to establish parameters qualification system on this animal model. Simutaneous evaluations of alcohol jaundice animal model and the efficacy of Zhizidahuang-Tang were on account of the classical Chinese Medicine rule “testing syndromes in formula”.

中医证候动物模型的制备水平是制约中药药性能否合理评价的关键，其直接影响药理活性结论的有效性。尽管学者们在中医酒疸动物模型研究上做了大量探索性工作,但所复制的动物模型是否表达了人体酒疸的表现特征,却被忽视。而且模型的评价指标常局限于从一个或几个疾病本身所表现出的现象中去选择，忽略了疾病对机体整体的影响。本课题以中医证候理论为指导，在对酒疸形成本质考察的基础上，复制“病”、“证”结合的酒疸动物模型。并引进代谢物组学的方法，从整体观出发，以机体代谢物组变化为载体，全面的解析疾病对机体的影响，从而选取能够表征机体整体状态的内源性动态代谢物作为模型的评价指标。通过治疗酒疸有效经典方剂栀子大黄汤对模型的影响，确证模型有效性。在此基础上，阐明酒疸形成的主要生物学基础及栀子大黄汤的治疗作用机理。

中医证候动物模型的制备水平是制约中药药性能否合理评价的关键，其直接影响药理活性结论的有效性。尽管学者们在中医酒疸动物模型研究上做了大量探索性工作,但所复制的动物模型是否表达了人体酒疸的表现特征,却被忽视。而且模型的评价指标常局限于从一个或几个疾病本身所表现出的现象中去选择，忽略了疾病对机体整体的影响。本课题以中医证候理论为指导，在对酒疸形成本质考察的基础上，复制了“病”、“证”结合的酒疸动物模型。并引进代谢物组学和蛋白质组学的方法，从整体观出发，以机体代谢物组和差异蛋白变化为载体，全面的解析疾病对机体的影响，从而选取能够表征机体整体状态的内源性生物标记物作为模型的评价指标。通过治疗酒疸有效经典方剂栀子大黄汤对模型的影响，确证了模型有效性。在此基础上，阐明了酒疸形成的主要生物学基础及栀子大黄汤的治疗作用机理。