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多角度、多方面对胆石成因及其机制进行探讨，但对胆汁代谢组学分析涉及甚少。课题组前期研究表明，大黄灵仙胶囊能有效防治胆结石，并发现其可能作用靶点；还借助核磁共振氢谱技术对胆石病模型动物进行血清代谢组学分析，发现血清脂质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胆结石的形成机制以及中药防治作用的靶点。本项目采用核磁共振氢谱技术结合免疫组化、Western-Blot等方法，分析胆石病模型豚鼠胆汁代谢组学特征以及肝细胞胆小管侧膜转运蛋白表达的改变，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 various directions and aspects to explore the causes and pathogenesis of gall-stone. However, little has been done on bile metabonomics analysis. Our research group found that Dahuanglingxian capsule was effective on cholelithiasis prevention and treatment, and potential targeting sites were suggested in research. Moreover, 1H-Nuclear Magnetic Resonance (1HNMR) was used in our research to analyze the serum metabonomics of cholelithiasisi model animals and found the relations between serum lipid metabolite and cholelithiasis. However, 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 1HNMR, immunohistochemistry, Western-Blot, and RT-PCR, to analyze the bile metabonomic characteristics of cholelithiasisi model and the protein expression changes of canalicular membrane transporters and to observe the intervention effects of Dahuanglingxian capsule. Through the comprehensive analysis of metabolizing information and biological events, the forming of gall-stone and the mechanism of Dahuanglingxian capsule for prevention and treatment of cholelithiasis will be further revealed, to provide a theory basis and research method for the application of combining Chinese medicine and western medicine for cholelithiasis prevention and treatment.