胆结石形成机制是胆道疾病的研究热点，而胆石病术后结石的残留与复发是临床医疗的难点。近年来国内外学者已从代谢组学、蛋白组学、基因组学等多角度、多方面对胆石成因及其机制进行探讨。课题组前期研究表明，大黄灵仙胶囊能有效防治胆结石。通过对胆石病模型动物血清、组织细胞等进行实验分析，发现多种基因表达通过调控血清代谢产物与胆结石形成的相关性。然而，胆结石的形成及中药复方的作用过程非常复杂，单一角度研究很难真正把握其形成机制以及作用靶点。本项目采用Western-Blot、RT-PCR、激光共聚焦、电镜、气相色谱-质谱联用技术等方法，分析兔胆石病模型核受体FXR系统蛋白表达以及胆汁代谢组学特征的改变，并在此基础上观察大黄灵仙胶囊的干预作用，通过综合分析代谢信息与生物学事件，进一步揭示胆结石形成和大黄灵仙胶囊防治胆结石的机制，为胆石病的中西医结合综合防治提供理论基础和研究思路。

Cholelithiasis pathogenesis is a research focus of cholangiopathy while postoperative calculus remaining and recurring being a major clinical problem.In recent years,researchers in China and overseas have studied from metabonomics,proteomics and genomics to explore the causes and pathogenesis of cholelithiasis. Our research group found that Dahuanglingxian capsule was effective on cholelithiasis prevention and treatment.We analyzed the experimental analysis of serum and tissue cells of cholelithiasisi model animals and found the correlation between serum metabolite and cholelithiasis. It is really difficult to reveal the pathogenesis of cholelithiasis and the targeting sites of Chinese medicine by researches only from one direction as the forming of gall-stone and acting process of complex prescription of Chinese herbs are both extremely complicated.This research program will apply western blot,RT-PCR,confocal laser scanning microscopy,1HNMR,immunohistochemistry,western blot,RT-PCR,electronic speculum,GC-MS to analyze the protein expression changes of FXR and the bile metabonomic characteristics of cholelithiasisi model.Observe the intervention effects of Dahuanglingxian capsule.We will analyze the metabolizing information and biological events,and reveal the reasoan of forming of cholelithiasis and the mechanism of Dahuanglingxian capsule for prevention and treatment of cholelithiasis.We plan to provide a theory basis and research method for the application of combining Chinese medicine and western medicine for cholelithiasis prevention and treatment.