课题组基于临床流行病学和数据挖掘技术研究非酒精性脂肪性肝（NAFL），提出"脾虚为本，湿热瘀血为标"的病机新模式，研制的降脂颗粒经临床及实验研究证实对改善NAFL具有良好效果，但具体机制尚未完全明确。法尼酯衍生物X受体(FXR)是调节胆汁酸代谢的关键代谢性核受体，新近研究证实胆汁酸-FXR信号在改善胆固醇转运、糖脂代谢、炎症调节中的发挥关键作用，参与调控NAFL相关的多条代谢通路，被认为是NAFL治疗的新靶点。本课题将从胆汁酸-FXR信号调节途径深入研究降脂颗粒对NAFL治疗机制，通过复制体内外NAFL模型，采用组织学、分子生物学、代谢组学等技术，从整体-组织-细胞三个层次探讨胆汁酸-FXR信号通路相关分子在NAFL进展中的动态变化，及降脂颗粒对这一通路相关分子的调节作用，预期研究结果对促进中医药防治NAFL、代谢综合征等胰岛素抵抗相关疾病有重要的基础及应用价值。

Based on our clinical investigations and data mining methods,we proposed a new Traditional Chinese Medicine (TCM) pathomechanism of Nonalcoholic Fatty Liver (NAFL): "Spleen-Deficiency as primary, Damp-Heat and Blood Stasis as secondary cause". Devised according to this theory, the herb formula Jiangzhi Granula showed benifits in treating NAFL and related metabolic disorders, but the mechanisms were not so clear. Farnesoid X receptor (FXR) blongs to ligand nuclear receptor class and involves in regulating bile acid metabolism, the bile acid activated FXR signaling plays critical roles of in improving cholesterol transport, lipid and glucose metabolism, inflammation, and other NAFL realting metabolic pathways, suggesting FXR could be a potential target for NAFL regression. This project aims to explore the potential mechanism of Jiangzhi Granula in regulating bile acid activated FXR signaling, through developing both animal and cell models, ustilizing tools such as histology, molecular biology, metabonomics et al, we will observe the dynamic changes of FXR signaling along with NAFL progress, and further investigate the influence of Jiangzhi Granula on these pathways. This project are expected to set fundamental modes for studying herb medicine in preventing and treating NAFL, metabolic syndrome and insulin resistance related diseases.