一氧化碳对缺氧性肺血管结构重建大鼠肺动脉内皮素-1表达的影响

Impact of carbon monoxide on endothelin-1 expression in pulmonary arteries of rats with hypoxic pulmonary vascular remodeling

目的探讨一氧化碳对缺氧性肺血管结构重建大鼠肺动脉中内皮素-1(ET-1)表达的影响。方法将大鼠随机分为3组:常氧组(n=15)、低氧组(n=15)和低氧+血红素加氧酶组(低氧+HO组)(n=15)。以光学显微镜观测3组大鼠肺中型动脉及小型动脉的相对中膜厚度(RMT)。应用ET-1的单克隆抗体经免疫组织化学技术对3组大鼠肺动脉ET-1进行定位及半定量分析。结果低氧组大鼠中型肺动脉及小型肺动脉RMT均高于常氧组和低氧+HO组(P<0.01)。3组大鼠各级肺动脉内皮细胞中均有ET-1的表达,低氧组高于常氧组和低氧+HO组(P<0.01)。中型肺动脉内皮细胞中ET-1的表达与相应中型肺动脉RMT之间呈正相关(r为0.8536,P<0.01);小型肺动脉内皮细胞中ET-1的表达与相应的小型肺动脉RMT之间呈正相关(r为0.8973,P<0.01)。结论一氧化碳对缺氧性肺血管结构重建大鼠肺动脉中ET-1表达有抑制作用。

Objective:To investigate the impact of endothelin-1 (ET-1) in the mechanisms by which carbon monoxide(CO) regulates hypoxic pulmonary vascular remodeling. Methods:36 rats were randomly divided into three groups: normoxic (n=15), hypoxic (n=15) and hypoxic+heme oxygenase (hypoxic+HO, n=15). The relative medial thickness (RMT) of small and medium muscularized pulmonary arteries was determined under light microscope. Immunohistochemical technique was used to assess the abundance and localization of ET-1 in pulmonary arteries.Results:RMT of small and medium pulmonary arteries in rats of hypoxic group was markedly higher than that of normoxic group and hypoxic+HO group(P < 0.01). ET-1 was expressed in pulmonary artery smooth muscle cells of three groups,more marked in hypoxic group than in normoxic group and hypoxic+HO group(P < 0.01)。There was a positive correlation between RMT and ET-1 expression in medium and small pulmonary arteries (r=0.8536 and 0.8973, P < 0.01 respectively).Conclusion:Carbon monoxide inhibited ET-1 expression by pulmonary arteries of rats with hypoxic pulmonary vascular remodeling.