Qingyou Zhang, Junbao Du, Weijin Zhou, Hui Yan, Chaoshu Tang, Chunyu Zhang
Department of Pediatrics, Peking University, First Hospital, Beijing 10034, PR China.
Biochem Biophys Res Commun. 2004 Apr 23;317(1):30-7. doi: 10.1016/j.bbrc.2004.02.176.
Hypoxic pulmonary hypertension (HPH) is an important pathophysiological process of a variety of cardiac and pulmonary diseases. But the mechanisms responsible for HPH are still not fully understood. The discoveries of endogenous gas signal molecules, nitric oxide (NO), and carbon monoxide (CO), have been moving the research of HPH to a new phase. Hydrogen sulfide (H2S), which is now being considered as the third new gas transmitter, was found to be possibly involved in the pathogenesis of HPH. But whether there exists an interaction between H2S and CO has not been clear in the pathogenesis of HPH. In this study, we found that H2S was significantly decreased in the pathogenesis of HPH. However, plasma CO level and the expressions of heme oxygenase (HO-1) protein and HO-1 mRNA were significantly increased. Exogenous supply of H2S could alleviate the elevation of pulmonary arterial pressure. At the same time, plasma CO level and the expressions of HO-1 protein and mRNA in pulmonary arteries were significantly increased. Whereas, exogenous supply of propargylglycine (PPG), an inhibitor of cystathionine gamma-lyase (CSE), decreased the plasma H2S content and worsened HPH. At the same time, plasma CO level and the expressions of HO-1 protein and mRNA in pulmonary arteries were decreased. The results showed that H2S could play a regulatory role in the pathogenesis of HPH through up-regulating CO/HO pathway.
低氧性肺动脉高压（HPH）是多种心肺疾病的重要病理生理过程。但其发病机制仍未完全明确。内源性气体信号分子一氧化氮（NO）和一氧化碳（CO）的发现，使HPH的研究进入了一个新阶段。硫化氢（H2S）现被认为是第三种新型气体递质，发现其可能参与HPH的发病机制。但在HPH发病机制中，H2S与CO之间是否存在相互作用尚不清楚。在本研究中，我们发现H2S在HPH发病机制中显著降低。然而，血浆CO水平以及血红素加氧酶（HO-1）蛋白和HO-1 mRNA的表达显著增加。外源性补充H2S可减轻肺动脉压力升高。同时，血浆CO水平以及肺动脉中HO-1蛋白和mRNA的表达显著增加。而补充胱硫醚γ-裂解酶（CSE）抑制剂炔丙基甘氨酸（PPG）则降低了血浆H2S含量并加重了HPH。同时，血浆CO水平以及肺动脉中HO-1蛋白和mRNA的表达降低。结果表明，H2S可通过上调CO/HO途径在HPH发病机制中发挥调节作用。
