抗肝纤维化治疗可抑制慢性肝病向肝硬化发展，中医药是目前抗肝纤维化研究的焦点。经典方药桃红四物汤可抑制肝星状细胞激活以抗肝纤维化，而具体机制尚不明确。前期研究发现透明质酸合成酶2(HAS-2)与肝纤维化密切相关。在LX2细胞中抑制HAS-2表达，NOTCH3表达降低，LX2细胞活化被抑制；且桃红四物汤抑制LX2活化时HAS-2、NOTCH3表达降低。因此，本项目基于桃红四物汤“扶正补虚，活血化瘀”的中医理论，结合经典信号通路NOTCH3及前期研究桃红四物汤对HAS-2、NOTCH3表达的初步探索，提出“桃红四物汤调控HAS-2/NOTCH3信号通路抗肝纤维化”的科学假说。为此，扩大临床样本量，复制四氯化碳肝纤维化模型，结合体外细胞培养，从体内-细胞-分子-基因多层次阐明桃红四物汤抑制HAS-2调控NOTCH3以抗肝纤维化的机制，为桃红四物汤临床防治肝纤维化提供理论依据。

Anti-fibrosis treatment can inhibit the development of chronic liver disease to cirrhosis, Traditional Chinese medicine is the focus of anti-liver fibrosis research. The classic prescription Tao Hong Si Wu Decoction(THSWD) can inhibit the hepatic stellate cell activation to against liver fibrosis, but the specific mechanism is not clear. Our previous studies found that hyaluronan acid synthase 2 (HAS-2) is closely related to the development of liver fibrosis. When the HAS-2 were inhibited in the LX2, NOTCH3 expression decreased, LX2 cell activation also was inhibited; The HAS-2 and NOTCH3 expression decreased when THSWD inhibit LX2 activation. Therefore, this project is based on the TCM theory of "promoting blood circulation and removing blood stasis", combined with the classic signal pathway NOTCH3 and the preliminary study of THSWD on the expression of HAS-2 and NOTCH3, to propose the anti-fibrosis hypothesis that the THSWD regulates the HAS-2/NOTCH3 signaling pathway. In order to prove this hypothesis, we continue to expand the clinical sample volume, replication of carbon tetrachloride liver fibrosis model, combined with in vitro cell culture, from the in vivo-cell-molecule-gene multilevel to elucidate the mechanism that THSWD inhibit HAS-2 regulation of NOTCH3 to anti-liver fibrosis. It will provide a theoretical basis for THSWD treatment of liver fibrosis in the clinical.