从肠源性内毒素血症诱导肝星状细胞NF-κB的活化探讨大黄蜇虫丸抗肝纤维化机制

肝星状细胞（HSC）的活化是肝纤维化发生发展的中心环节。肠源性内毒素血症的主要成分脂多糖（LPS），通过Toll-like受体4（TLR4）活化HSC核转录因子NF-κB，进而使转化生长因子（TGF）-β的假受体骨成形蛋白-激活素膜结合阻断因子（BAMBI）表达降低，增加了HSC对TGF-β的敏感性，从而产生肝纤维化。大黄蛰虫丸临床广泛用于肝纤维化的治疗，但其机制仍不十分明确。本项目拟从大黄蛰虫丸抑制HSC细胞LPS-TLR4-NF-κB-BAMBI通路角度探讨大黄蛰虫丸抗纤维化的分子机制。项目拟在纤维化大鼠、大鼠原代HSC和HSC-T6细胞系上，用Westernblot、免疫组化、腺病毒感染、RNA干扰、激光共聚焦显微镜、电镜检测等方法，检测大黄蛰虫丸对这条通路相关分子表达的变化，从分子水平认识大黄蛰虫丸治疗肝纤维化的有效靶点和分子机理，为传统中医药进一步的开发奠定理论基础。

The activation of Hepatic stellate cells (HSC) is the center process of liver fibrogenesis. Intestinal endotoxin whose major content is lipopolysaccharide (LPS), can activate NF-κB of HSC through Toll-like receptor 4 (TLR4), promote nuclear transcription factor NF-κB activation, leading to the decrease of BMP and the activin membrane-bound inhibitor (BAMBI), that is a pseudo-receptor of transforming growth factor-β(TGF-β). Dahuangzhechongwan (DHZCW), that is a traditional Chinese medicine, has been used to therapy liver fibrosis in clinic patients, but the mechanism was not been elucidated clearly. This process must increase the sensitivity of HSC to TGF-βand further more, promote fibrogenesis. This project will study the molecular mechanism of DHZCW anti-fibrosis by pathways of LPS-TLR4-NF-κB-BAMBI. By way of immunohistochemistry stain, Westernblot, RNAi and adenovirus infection and confocal microscopy, the change of each upper-stream molecular of BAMBI will be observe in liver fibrosis rats, primary HSC cells and HSC-T6 cell line after DHZCW treatment. This project is to illuminate the molecular mechanism of DHZCW treating liver fibrosis and will be benefit for exploiting traditional Chinese medicine.