气体信号分子在肺动脉高压发病中的作用

肺动脉高压是临床众多心肺血管疾病发生、发展中重要的病理过程,决定疾病的进展及预后.肺动脉高压又是复杂病理过程,其发病机制迄今尚未完全阐明.气体分子一氧化氮(NO)和一氧化碳(CO)以其特有的可连续产生、传播迅速、效应广泛等特点对肺循环的作用与其他器官相比更具有特殊意义,并引起科学界的广泛关注,从而开创了气体信号分子这一崭新研究领域.一直被称为有毒废气的硫化氢(H2S)可在机体内源性生成,本课题组研究了H2S在心血管系统的合成与分布、心血管生理学以及病理生理学意义,提出内源性H2S是心血管功能调节的新型气体信号分子,并揭示其对心血管疾病发病具有普遍性调节作用.通过对这3种气体信号分子在低氧性和高肺血流性肺动脉高压中的变化规律、作用环节及其分子机制的研究发现,气体信号分子体系异常是这两种肺动脉高压发病中重要发病机制之一,外源性给予气体信号分子可以缓解肺动脉高压和肺血管结构重建,其作用机制包括舒张血管、调节血管平滑肌细胞增殖/凋亡失衡、通过抑制胶原蛋白过度合成、促进胶原蛋白降解环节抑制肺动脉胶原蛋白的异常堆积,进而揭示了气体信号分子在肺动脉高压中的重要调节作用.

Role of gasotransmitters in the pathogenesis of pulmonary hypertension

Pulmonary hypertension is a complicated and important pathological process in the development of a variety of cardiovascular and pulmonary diseases, and directly affects the development of the diseases and their prognosis. but its mechanisms are still not fully understood. Therefore, to clarify the mechanisms is an important task in this field. Nitric oxide (NO) and carbon monoxide (CO) have special significance in pulmonary circulation as compared with other organs for their special biological properties including continuous production, fast transmission and extensive action, etc, which attracts great attention in the life science research and initiates the new research field of gasotransmitters. Hydrogen sulfide (H_2S), which has been recognized as a toxic gas, can be endogenously produced in the body. We considered it to be a new cardiovascular regulatory gasotransmitter based on the studies of its synthesis and distribution in cardiovascular system and cardiovascular effects under physiologic and pathophysiologic conditions. We found it exerted a general regulatory significance in cardiovascular diseases. Based on the research of the three gasotransmitters in hypoxic and high pulmonary blood flow-induced pulmonary hypertension, it was found that the dysfunction of the gasotransmitter pathways was involved in the pathogenesis of pulmonary hypertension and the supplement of gasotransmitters could alleviate pulmonary hypertension and pulmonary vascular remodeling. The mechanisms included that they could regulate vessel dilation, correct the imbalance between smooth muscle cell proliferation and apoptosis, inhibit the excess synthesis and stimulate the degradation of collagen, therefore inhibiting abnormal accumulation of collagen, etc. All these results indicated the significant regulatory effects of gasotransmitters in the pathogenesis of pulmonary hypertension.