肝纤维化是由多种病因引起的慢性肝损伤的共同病理改变，目前尚无理想的治疗药物。已知肝星状细胞(HSCs)的活化是纤维化的中心环节，成纤维细胞生长因子受体FGFRs在HSCs中为高表达，而我们前期研究也发现FGFRs在肝纤维化前期髓源抑制细胞MDSCs（CD11b+Gr-1+）中高表达，且持续激活的FGFR1可促进肝纤维化的发生。由此我们推测FGFR1可能为肝纤维化的治疗靶点。我们前期经设计、合成及体外筛选得到的新型小分子化合物SKLB-611能有效抑制FGFR1活性和HSCs增殖，还可以减少肝纤维化前期MDSCs数量等。本课题拟在此基础上，进一步研究SKLB-611对激活的HSCs及体内治疗肝纤维化的作用与分子机制，特别深入研究SKLB-611作用于肝纤维化前期MDSCs及通过抑制FGF/FGFR信号通路抗肝纤维化的潜在机制。本课题将为基于FGF/FGFR信号通路等抗肝纤维化研究提供新思路。

Hepatic fibrosis is a common pathological change of chronic liver injury caused by various causes. Nowadays, there is currently no clinical cure for hepatic fibrosis. The activation of hepatic stellate cells (HSCs) is a key step in hepatic fibrosis, and (fibroblast growth factor receptors, FGFRs) were highly expressed in HSCs. Our previous studies also found that FGFRs was highly expressed in MDSCs (Myeloid-derived suppressor cells, CD11b+Gr-1+) at the early stage of hepatic fibrosis, and continuous activation of FGFR1 could promote the occurrence of hepatic fibrosis. Therefore, we speculate that FGFR1 may be a therapeutic target for hepatic fibrosis. After our previous design, synthesis and in vitro screening, we found the compound SKLB-611 could inhibit effectively the activities of FGFR1 kinase and the proliferation of HSCs. Moreover, SKLB-611 also reduced the numbers of MDSCs in the early stage of hepatic fibrosis. Base on the preliminary study, this study will explore the potential molecular mechanism of SKLB-611 effect on activated HSCs, and further investigate the effects of SKLB-611 on hepatic fibrosis in vivo. We will investigate the effects of SKLB-611 on MDSCs and clarify the underlying mechanism of anti-hepatic fibrosis through FGF/FGFR signaling pathway inhibition. This study will provide a novel therapeutical idea for hepatic fibrosis.