成纤维细胞生长因子21（FGF21）的血管保护作用近年来备受关注，其在体循环中可保护血管内皮细胞，抑制血管平滑肌细胞增殖，但在肺循环中作用不明。项目组前期研究发现外源性给予FGF21可改善低氧肺动脉高压大鼠肺血管重构及肺动脉高压，并上调PPARγ。据报道激活PPARγ可抑制肺动脉高压，改善肺血管重构。结合文献及我们的前期研究发现，AMPK通路及miR-27b可能参与FGF21对PPARγ的调控。本研究拟外源性给予FGF21及FGF21基因敲减，上下调干预AMPK，并构建miR-27b过表达和敲减模型，通过离体研究探索FGF21是否通过AMPK通路及miR-27b途径上调PPARγ，从而抑制肺动脉高压。并拟进一步采用FGF21KO小鼠模型，在整体层面研究上述不同干预对肺动脉压力、肺血管重构、肺血管炎症的影响。本项目将为开发肺动脉高压防治的新型药物、探索肺动脉高压防治新靶点提供实验依据。

There is a growing interest in the vascular protection of fibroblast growth factor 21（FGF21）. Recent reports showed FGF21 could protect vascular endothelial cells and inhibit the proliferation of vascular smooth muscle cells in systemic circulation. However, the effects of FGF21 in pulmonary circulation are unclear. Our previous research showed that hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in rats were attenuated after FGF21 treatment, simultaneously the level of peroxisome proliferator-activated receptors γ(PPARγ) was elevated. It is reported that up-regulating PPARγ can suppress pulmonary hypertension and alleviate pulmonary vascular remodeling. Based on recent studies and our previous researches, we find AMPK pathway and miR-27b may be involved in the regulation of FGF21 and PPARγ. This project intends to study the role of FGF21 in pulmonary hypertension induced by hypoxia, and to further investigate whether FGF21 can suppress pulmonary hypertension and pulmonary vascular remodeling by up-regulating PPARγ via AMPK pathway and miR-27b by in vitro and in vivo study. FGF21 treatment, FGF21 gene knockdown, up-regulation and down-regulation of AMPK pathway, miR-27b overexpression and knockdown models will be performed in vitro research. In this study, FGF21 knockout mice model will be established in vitro to investigate whether AMPK pathway and miR-27b could affect FGF21, PPARγ, pulmonary artery pressure, pulmonary vascular remodeling and inflammation in hypoxia-induced pulmonary hypertension mice. This study will be helpful in finding a new drug with good efficacy and finding a potential novel way to treat pulmonary hypertension.