二氧化硫调节钙敏感蛋白受体对低氧性肺动脉高压肺动脉平滑肌细胞的作用及机制研究

Hypoxia could upregulate the expression of calsium-sensing receptor (CaSR) that increased intracellular calcium (Ca2+) concentration，contributing to cell conversion from contractile type to synthetic, and increased cell migration from medial to intimal, leading to hypoxic pulmonary vascular remodeling. Recent studies have reported endogenous generation of the novel gasotransmitter, sulfur dioxide (SO2). SO2 decreased pulmonary artery pressure, relieved vascular remodeling, and downregulated myocardial intracellular Ca2+ concentration in rats with hypoxic pulmonary hypertension (HPH). Our research suggested that SO2 attenuated HPH induced vascular remodeling, implying new therapy for HPH. However, the molecular mechanism of SO2 regulating HPH remains unknown. Preliminary research showed that SO2 regulated CaSR expression in pulmonary artery smooth muscle cells (PASMc). Therefore, we hypothesized that SO2 inhibited CaSR gene and protein expression, downregulated intracellular Ca2+ concentration，and attenuated vascular remodeling in HPH. This study investigated the in vivo and in vitro effect of SO2 on CaSR gene and protein expression in PASMC from rats with HPH. Further, explored the feasibility of SO2 therapy in HPH and potentialize new therapy target for HPH.

低氧诱导钙敏感受体(CaSR)表达增强，引起肺动脉平滑肌细胞(PASMc)内钙离子(Ca2+)浓度上升，导致细胞由收缩型向合成型转化，从中膜迁移至内膜大量增殖，是低氧性肺动脉高压(HPH)血管重塑的重要原因。近年来研究发现机体中存在新型气体信号分子二氧化硫(SO2)内源性生成体系，SO2能降低HPH大鼠肺动脉压力，减少心肌细胞内Ca2+浓度增加。我们前期研究表明SO2可以改善HPH所致的血管重塑, 可能为防治HPH提供新途径，但其机制并不清楚。进一步实验发现SO2可以调节PASMc CaSR的表达，推测SO2可能通过抑制CaSR基因及蛋白表达，缓解细胞内Ca2+浓度升高，改善肺动脉高压所致的血管重塑。本研究通过细胞和整体水平研究SO2对HPH肺动脉平滑肌细胞CaSR表达的影响，以及SO2对HPH肺动脉平滑肌细胞的影响，探讨SO2治疗HPH的可行性，为临床HPH的防治提供理论基础和实验依据。