小肠胆固醇吸收在胆囊结石形成中作用的分子学机制的研究，是国内外胆石成因研究领域的热点问题。前期研究证实，NPC1L1是小肠粘膜重要的胆固醇转运载体，抑制其功能，可以降低小肠胆固醇吸收，对胆囊胆固醇结石的预防和治疗具有重要意义。SREBP-2是调控NPC1L1表达的重要因子，姜黄素可以下调SREBP-2的表达，间接抑制NPC1L1的活性，降低小肠胆固醇吸收。本项目旨在通过前期依折麦布预防饮食诱导的胆囊结石形成作用的研究基础上，通过转基因和基因敲除动物模型的建立，应用活体动物体内光学成像、Rt-PCR、电泳迁移率测定等技术，研究活体动物体内姜黄素对小肠胆固醇吸收的影响，探讨姜黄素干预下小肠上皮SREBP-2表达水平和NPC1L1活性变化，阐明姜黄素降低血清胆固醇及预防胆囊结石形成的分子学机制，为胆囊胆固醇结石病的早期预防和药物治疗提供可靠的实验依据。

Nowadays, intestinal cholesterol absorption in the molecular mechanism of gallstone formation is a hot issue in the research of cholelithiasis. Studying the regulation factor of intestinal cholesterol absorption has a great significance for the prevention and treatment of cholesterol gallstone. NPC1L1 is the cholesterol transporter in intestinal epithelium, which is regulated by SREBP-2. Curcumin can down-regulate the expression of SREBP-2 and inhibit the NPC1L1 activity, then decrease the absorption of intestinal cholesterol. In preliminary study, we found EZET can prevent the formation of cholesterol gallstone. Based on this founding, we study the affection of curcumin to intestinal cholesterol absorption on transgenic and gene knockout animal models by optical in vivo imaging, Rt-PCR and gel shift assay. By exploring SREBP-2 mediates the modulation of intestinal NPC1L1 expression by curcumin, we want to clarify the mechanism of curcumin decreasing blood cholesterol and preventing the formation of gallstone, which can provide reliable experimental evidence for cholesterol gallstone clinic early prevention and drug treatment.