内源性一氧化氮与硫化氢在大鼠低氧性肺动脉高压中的相互作用

目的:研究一氧化氮(nitric oxide,NO)/一氧化氮合酶(nitric oxygnase, NOS)体系和硫化氢(hydrogen sulfide,H2S)/胱硫醚γ-裂解酶(cystathionine-γ-lyase,CSE)体系在低氧性肺动脉高压发生机制中的作用及其相互关系.方法:将25只大鼠随机分为4组:低氧组(7只)、低氧 L-NAME组(给与NOS抑制剂Nω-硝基-L-精氨酸甲酯处理的低氧组,6只)、低氧 PPG组(给与CSE抑制剂炔丙基甘氨酸处理的低氧组,6只)和对照组(6只).低氧21 d后,测定肺动脉平均压、血浆NO及H2S含量,分别测定低氧组、低氧 L-NAME组及对照组CSE活性,应用免疫组织化学的方法检测低氧组、低氧 PPG组及对照组的肺动脉内皮细胞eNOS表达.结果:低氧21 d大鼠肺动脉平均压力明显增高,同时血浆中NO和H2S含量、肺动脉内皮细胞eNOS表达及肺组织CSE活性亦明显下降;而低氧 L-NAME组,伴随着NO含量的下降,肺动脉平均压显著上升,同时,血浆中的H2S含量及肺组织CSE活性较低氧组显著上升;在低氧 PPG组,伴随血浆H2S含量的降低,肺动脉压力显著升高,同时血浆中的NO含量及肺血管内皮细胞eNOS表达也较低氧组显著上升.结论:内源性NO/NOS体系与H2S/CSE体系在低氧性肺动脉高压中呈现相互的负性调节作用.它们既相互独立又以网络调节的方式共同参与低氧性肺动脉高压形成的调控机制.

Interaction between endogenous nitric oxide and hydrogen sulfide in pathogenesis of hypoxic pulmonary hypertension

OBJECTIVE: To investigate the interaction between nitric (NO) / nitric oxygenase (NOS) and hydrogen sulfide (H(2)S)/ cystathionine-gamma-lyase (CSE) system in the pathogenesis of hypoxic pulmonary hypertension. METHODS: 25 rats were randomly divided into four groups: hypoxic group (n=7 ), hypoxic + L-NAME group (n=6 ), hypoxic + PPG group (n=6) and control group (n=6 ). After 21 days, pulmonary artery mean pressure (mPAP) of each rat was evaluated, and the plasma concentration of H(2)S and NO was measured. Meanwhile, the activities of CSE in pulmonary tissue in hypoxic, hypoxic + L-NAME and control groups were detected, respectively, and expressions of NOS in pulmonary arteries in hypoxic, hypoxic + PPG and control groups were also detected by immunohistochemistry technique. RESULTS: mPAP was significantly increased in hypoxic rats as compared with normal controls. Meanwhile, compared with controls, the production of NO and H(2)S in plasma, the activity of CSE in pulmonary tissue and expression of NOS in pulmonary arteries were markedly decreased in hypoxic rats. However, mPAP was significantly increased in hyopxic + L-NAME group as compared with hypoxic groups, and at the same time, the plasma concentration of NO was markedly decreased. However, the plasma concentration of H(2)S and the activity of CSE in pulmonary tissue in hyopxic+L-NAME group were increased significantly as compared with those of hypoxic group. PPG also worsened pulmonary hypertension of hypoxic rats, however,it increased endogenous production of NO and the expression of NOS of pulmonary arteries obviously. CONCLUSION: There is a negative feed back effect between NO/NOS system and H(2)S/CSE system in development of hypoxic pulmonary hypertension. They might interact with each other and therefore play an important regulating role in hypoxic pulmonary hypertension.