Galectin-3调节外膜功能在肺动脉高压血管重构中的作用及机制研究

Pulmonary Hypertension is a severe progressive disease with poor prognosis, the pathobiological mechanism of which is now still incompletely understood. Accumulating evidence suggests that, adventitia, especially adventitial fibroblasts interacting with ECM, plays an essential role in the pulmonary vascular remodeling. Furthermore, Gal3, acting as a multifunctional profibrotic factor, can regulate fibroblasts in different way. Our previous work has shown that Gal3 is noticeably upregulated both in the PA adventitia of hypoxia rats and in the adventitial fibroblasts under hypoxia condition, which consists with recent literatures. However the precise role of Gal3 in the remodeling of pulmonary arteries is still obscure. Therefore, initially, we try to further confirm the relationship between Gal3 and adventitial fibroblast as well as its role in PH related ECM changes. The experiment will be conducted in cells, animals and patients. Plus,we will also try to clarify the mechanism of the regulatory role of Gal3 in adventitial fibroblasts and ECM in our research. Finally we are going to ellucidate the possibilty of Gal3 becoming a potential biomarker for the diagnosis and treatment of PAH.

肺动脉高压（PH）是一类严重疾病，病程进展迅速且预后不佳。血管重构作为PH重要病理特征其内在机制仍欠清晰。研究表明外膜在血管重构中的作用明显，其中成纤维细胞通过功能改变及与细胞外基质发生相关作用参与血管重构的产生。而Galectin3作为一种促纤维因子对成纤细胞调控作用明显。本课题组前期动物实验中发现低氧条件下PH大鼠肺动脉管外膜Galectin3水平显著上调，其肺组织Galectin3水平同样升高；细胞实验中低氧诱导大鼠肺动脉外膜成纤维细胞Galectin3上调显著。而给予Galectin3抑制剂可逆转其增殖效应。因此我们认为Galectin3可能通常调节外膜功能参与PH血管重构。本研究拟在此基础上从细胞、动物、患者三水平入手，深入阐述Galectin3调节外膜功能及参与肺血管重构的相关机制，并进一步探讨Galectin3作为新型生物学标记物在肺动脉高压中的临床转化价值。

肺动脉高压（PH）是一类严重疾病，病程进展迅速且预后不佳。血管重构作为PH重要病理特征其内在机制仍欠清晰。研究表明外膜在血管重构中的作用明显，其中成纤维细胞通过功能改变及与细胞外基质发生相关作用参与血管重构的产生。而Galectin3作为一种促纤维因子对成纤细胞调控作用明显。本课题组前期动物实验中发现低氧条件下PH大鼠肺动脉管外膜Galectin3水平显著上调，其肺组织Galectin3水平同样升高；细胞实验中低氧诱导大鼠肺动脉外膜成纤维细胞Galectin3上调显著。而给予Galectin3抑制剂可逆转其增殖效应。因此我们认为Galectin3可能通常调节外膜功能参与PH血管重构。本研究拟在此基础上从细胞、动物、患者三水平入手，深入阐述Galectin3调节外膜功能及参与肺血管重构的相关机制，并进一步探讨Galectin3作为新型生物学标记物在肺动脉高压中的临床转化价值。