低氧环境下温阳化浊通络方调控内皮细胞线粒体自噬和EndoMT改善SSc肺微血管损伤的作用机制

肺血管损伤是影响系统性硬化病（SSc）进展和预后的主要原因之一。研究证实肺微血管内皮细胞损伤的机制主要与缺氧、炎症、自噬过度及内皮-间充质转化（EndoMT）等相关。研究发现，低氧环境下HIF-1α/BNIP3/PINK1/Parkin轴介导的内皮细胞线粒体自噬和HIF-1α/Foxm1/Smad轴介导的EndoMT均与SSc肺微血管损伤密切相关。前期研究表明，温阳化浊通络方治疗SSc临床效果显著，能够保护血管，改善微循环。本项目拟从体外SSc肺微血管内皮细胞水平和SSc动物模型整体水平，探索温阳化浊通络方分别通过调控HIF-1α/BNIP3/PINK1/Parkin和HIF-1α/Foxm1/Smad轴干预内皮细胞线粒体自噬和EndoMT的作用环节与靶点，明确其干预SSc肺微血管损伤的全新作用机制，为温阳化浊通络方用于治疗SSc提供科学实验依据，也为中医药治疗SSc提供新的思路。

Pulmonary vascular injury is one of the main reasons affecting the progress and prognosis of systemic sclerosis (SSc). Studies have confirmed that the mechanism of lung microvascular endothelial cell injury is mainly related to hypoxia, inflammation, excessive autophagy, and endothelial-mesenchymal transition (EndoMT). Studies found that endothelial cell mitophagy mediated by HIF-1α/BNIP3/PINK1/Parkin axis and EndoMT mediated by HIF-1α/Foxm1/Smad axis are closely related to SSc pulmonary microvascular injury under hypoxic condition. Previous studies have shown that Wenyang Huazhuo Tongluo Formula has a significant clinical effect on SSc, which can protect blood vessels and improve microcirculation. In SSc lung microvascular endothelial cells and SSc animal models, this project intends to explore the roles and targets of Wenyang Huazhuo Tongluo Formula to intervene endothelial mitophagy and EndoMT by regulating HIF-1α/BNIP3/PINK1/Parkin and HIF-1α/Foxm1/Smad axis, clarify its new mechanism of intervention for SSc lung microvascular injury, provide scientific experimental basis for Wenyang Huazhuo Tongluo Formula treating SSc, and also provide new ideas for the treatment of SSc with traditional Chinese medicine.