肝纤维化是各种慢性肝病治疗过程中的重点和难点，目前尚缺乏高效的药物。湿热瘀毒是肝纤维化发生的主要病因，黄芩具有清热燥湿、泻火解毒的功效，常用于治疗湿热瘀毒所致的肝胆系统疾病。前期研究发现黄芩主要活性成分汉黄芩素能明显缓解胆汁淤积型（BDL）肝纤维化大鼠模型的肝纤维化程度，促进大鼠肝星状细胞系HSC-T6的衰老。RNA-seq比较汉黄芩素处理HSC-T6组与对照组的基因表达差异，发现PML的表达量在衰老的HSC-T6中显著上调，进一步发现下游p53蛋白K120残基乙酰化水平增加，p21转录增强。因此，我们提出汉黄芩素可能通过调控PML/p53信号轴介导的肝星状细胞衰老抑制肝纤维化。本课题拟采用原代肝星状细胞及BDL和CCl4致肝纤维化动物模型，从细胞和个体水平系统阐释汉黄芩素抑制肝纤维化的分子机制，为肝纤维化防治策略提供新的选择。

Hepatic fibrosis is the emphasis and difficulty in the treatment process of various chronic hepatic diseases and there still lacks effective therapeutic medicine at present. Hepatic fibrosis is mainly caused toxin generated by accumulation of Damp-Heat. Scutellaria baicalensis Georgi is important therapy medicine for hepatobiliary disease for its characteristic of Heat-cleaning, Damp-eliminating and Detoxicating. By using rat hepatic fibrosis model caused by Bile Duct Ligation (BDL), we found wogonin could significantly alleviate hepatic fibrosis. Meanwhile, wogonin could increase cellular senescence of rat hepatic stellate cell line (HSC-T6). When analyzing RNA sequencing (RNA-seq) data of wogonin-treated and control groups, we found Promyelocytic leukemia protein (PML) was up-regulated in senescent HSC-T6 cells treated by wogonin. Further study demonstrated wogonin increased acetylation level of p53 at K120 site, and up-regulated the transcription of p21. We therefore hypothesize that wogonin regulates hepatic stellate cell senescence through PML/p53 signaling axis to inhibit hepatic fibrosis. The primary hepatic stellate cell and BDL and CCl4-hepatic fibrosis rat models will be used to uncover the underlying anti-fibrosis mechanism of wogonin in vitro and in vivo. The results generated by this project will provide a new strategy choose for prevention and curation of hepatic fibrosis.