肺动脉高压形成机制中的气体信号分子网络

目的:肺动脉高压的形成机制至今还不清楚.近年来我们围绕气体信号一氧化氮及一氧化碳调节网络在肺动脉高压形成机制中的作用开展了系列研究.方法:低氧性肺动脉高压及高肺血流性肺动脉高压动物模型的建立,血流动力学测定,血管环舒张反应研究,肺动脉超微及显微结构研究,分子生物学,免疫细胞化学,免疫组织化学,流式细胞术,生物化学,肺动脉平滑肌细胞及内皮细胞培养等.结果:一氧化氮、一氧化碳及其调节网络在肺血管结构重建、肺动脉高压形成中发挥重要作用.二者参与对肺动脉平滑肌细胞增殖的抑制作用及凋亡的促进作用,证明二者对肺动脉高压时胶原堆积具有抑制作用.研究同时发现,二者对平滑肌细胞增殖促进因子的抑制作用以及对平滑肌细胞增殖抑制因子的促进作用参与其对肺血管结构重建、肺动脉高压形成的调节.结论:一氧化氮、一氧化碳及其调节网络在肺动脉高压的形成中发挥重要作用.

The regulatory network of gaseous molecules in the development of pulmonary hypertension

Objective: To explore the role o f regulatory network of gaseous molecules, nitric oxide (NO) and carbon monoxide (CO) in the development of pulmonary hypertension and its mechanisms. Methods: The following methods were utilized in the studies, including establishment of r at models of hypoxic pulmonary hypertension and high pulmonary blood flow-induc e d pulmonary hypertension, hemodynamic measurement, test of vasorelaxation of vas cular rings, micro- and ultra-structural analysis, molecular biology, immunocy to chemisty, immunohistochemistry, flow-cytometry, biochemistry, pulmonary smooth m uscle cell and endothelial cell cultures, etc. Results: NO and CO as well as the ir regulatory network played an important role in the development of pulmonary v ascular structural remodeling and pulmonary hypertension. These two gaseous mole cules were involved in the inhibition of pulmonary smooth muscle cell proliferat ion and stimulation of its apoptosis could significantly inhibit the accumulation of collagens in the regu lation of pulmonary hypertension. Furthermore, the inhibiting effect of gaseous mole cules on vascular smooth muscle cell proliferation promotersand the promoting e ffect on vascular smooth muscle cell proliferation inhibitors might be involved in the regulation of pulmonary vascular structural remodeling and pulmonary hype rtension. Conclusion: NO, CO and the gaseous molecular regu latory net work played an important role in the development of pulmonary hypertension.