Kca3.1介导的线粒体自噬调控低氧性肺血管重塑的机制研究

肺动脉高压（PAH）是多种肺部疾病的终末阶段，死亡率高，发病机制尚不明确。肺动脉平滑肌细胞（PASMC）增殖导致的肺血管重塑是PAH发生发展的重要原因。Kca3.1促进低氧性PASMC增殖，参与调节线粒体自噬相关分子的表达。为进一步研究Kca3.1参与PAH肺血管重塑及相关调控机制，在前期基础上，本研究拟通过构建低氧诱导的原代大鼠PASMC增殖模型以及大鼠PAH模型，采用特异性抑制剂、siRNA干预Kca3,1，通过体内体外实验，探讨1）Kca3.1介导的线粒体自噬调控低氧性PASMC增殖的机制研究；2）Kca3.1在大鼠低氧性肺血管重塑中的作用机制研究；3）靶向干预Kca3.1对PAH肺血管重塑治疗的作用，为肺血管重塑治疗提供新靶点，为PAH治疗提供新的靶向治疗。

Pulmonary artery hypertension (PAH) is the end-stage of various lung diseases with high mortality and undefined pathogenesis. Pulmonary artery remodeling induced by pulmonary artery smooth muscle cell proliferation (PASMC) plays a key role in the initiation and development of PAH. Overexpression of Kca3.1 contributes to hypoxia-induced PASMC proliferation and regulates the expression of mitophagy proteins. To evaluate the regulation role of Kca3.1 in PAH artery remodeling and the possible mechanisms, we establish hypoxia-induced rat PAH models and PAMSC and specific Kca3.1 inhibitor and siRNA in vitro/vivo to study 1) the mechanisms of Kca3.1-induced mitophagy in PAMSC proliferation, 2) the mechanisms of Kca3.1 in hypoxic pulmonary artery remodeling in rat and 3) the effects of targeted intervention of Kca3.1 on hypoxic PAH. This study aims to offer the possibility that Kca3.1 could be a new therapeutic target for hypoxic pulmonary artery remodeling and provides new targeted therapy for PAH.