缺氧性肺动脉高压时一氧化氮合酶、左旋精氨酸及亚硝基左旋精氨酸甲酯的研究

目的研究一氧化氮（ＮＯ）在缺氧性肺动脉高压（ＨＰＨ）发病中的作用。方法用烟酰胺腺嘌呤二核苷酸磷酸—黄递酶（ＮｉｃｏｔｉｎａｍｉｄｅＡｄｅｎｉｎｅＤｉｎｕｃｌｅｏｔｉｄｅＰｈｏｓｐｈａｔｅＤｉａｐｈｏｒａｓｅ，ＮＡＤＰＨｄ）和免疫组化ＡＢＣ方法检测原生型和诱生型一氧化氮合酶（ｃＮＯＳ、ｉＮＯＳ）在正常和缺氧大鼠肺内的表达和分布，同时观察左旋精氨酸（Ｌａｒｇ）和亚硝基左旋精氨甲酯（ＬＮＡＭＥ）对正常和缺氧大鼠肺循环的影响。结果ＨＰＨ组，ＮＡＤＰＨｄ阳性反应见于大血管内皮、平滑肌、支气管粘膜上皮及小血管内皮和平滑肌中，而后者在正常时未见阳性反应；ｃＮＯＳ在肺血管内皮和支气管粘膜上皮中的表达明显减弱，甚至消失，而正常时不表达ｉＮＯＳ的肺血管内皮和血管、支气管平滑肌在ＨＰＨ组出现了阳性表达；缺氧时补充Ｌａｒｇ和ＬＮＡＭＥ，与单纯缺氧相比，对右心室肥大和肺血管重建无影响。结论缺氧时ｃＮＯＳ被抑制，可能对ＨＰＨ的形成具有一定的作用；而ｉＮＯＳ的诱导表达，则可能对ＨＰＨ的形成具有阻止作用。

Changes of nitric oxide synthase in hypoxic pulmonary hypertension and the effect of L arg and L NAME on pulmonary circulation

Objective To study the role of nitric oxide (NO) in Hypoxic pulmonary hypertension (HPH). Methods NADPH d and immunohistochemistry were used to study the expression and localization of constructive and inducible nitric oxide synthase (cNOS iNOS) in the lungs of normoxia and HPH rats, at the same time, the effects of L arginine (L arg) and nitro L arginine methyl ester (L NAME) on normoxic and hypoxic pulmonary circulation were investigated. Results NADPH d positive expression was detected in the endothelium and smooth muscle cells (SMC) of large pulmonary vessels (PV) and in the epithelium and SMC of bronchi in the HPH group, but negative in the endothelium and SMC of small PV in normoxia. Hypoxia not only inhibited the expression of cNOS in the endothelium and SMC of PV and epithelium of bronchi, but also induced the expression of iNOS in the endothelium and SMC of PV and SMC of bronchi. Administration of L NAME in normoxia had no effect on pulmonary circulation. The effect of administration of L arg and L NAME in hypoxia on right ventricular hypertrophy and remodeling of PV had no significance, compared with simple hypoxia. Conclusion The inhibition of cNOS may contribute to the occurance of HPH, but induced iNOS may depress the development of HPH.