【摘要】 目的　观察缺氧诱导因子 1α (HIF 1α)与诱导型一氧化氮合酶 (iNOS)基因在缺氧性肺动脉高压大鼠肺动脉的表达情况。方法常压间断缺氧法复制缺氧性肺动脉高压大鼠模型 ;右心导管测定平均肺动脉压 (mPAP) ;H·E染色观察肺血管重塑情况 ;原位杂交和免疫组织化学方法分别检测HIF 1α和iNOSmRNA及蛋白质。结果　缺氧 7天后大鼠mPAP升高 ,出现缺氧性肺血管重塑 (HPSR) ,缺氧 14天后出现右心室肥大。对照组大鼠肺动脉壁iNOS、iNOSmRNA、HIF 1αmRNA弱阳性 ,HIF 1α蛋白质在肺动脉内膜和中膜分别呈阴性和弱阳性 ;肺动脉壁iNOS蛋白质和mRNA表达水平于缺氧 3天增高 ,缺氧 7天上升达高峰 ,以后维持于高峰水平 ;HIF 1αmRNA表达水平于缺氧 14天以后显著升高 ;全部缺氧大鼠肺动脉内膜HIF 1α蛋白质强阳性 ,肺动脉中膜HIF 1α蛋白质表达水平于缺氧 3天上升达高峰 ,缺氧 14天以后逐渐向基线回降。缺氧条件下iNOS蛋白质水平与mPAP (r =0 74 ,P <0 0 1)和HPSR (r =0 78,P <0 0 1)呈正相关 ,与HIF 1α蛋白质水平呈负相关 (r =- 0 5 2 ,P <0 0 1)。结论　HIF 1α和iNOS均参与缺氧性肺动脉高压的发病 ,HIF 1α对iNOS可能具有转录激活作用 ,iNOS对HIF 1α的表达可能具有抑制作用更多还原

【Abstract】 Objective To observe the expression of hypoxia inducible factor 1alpha (HIF 1α) and inducible nitric oxide synthase (iNOS) genes in rat pulmonary artery in different phases of hypoxic pulmonary hypertension Method The rat madels of hypoxic pulmonary hypertension were established by normal pressure intermittent hypoxia The mean pulmonary arterial pressure (mPAP) was measured by right heart catheterization The hypoxic pulmonary vascular remodeling (HPSR) was analyzed with hematoxylin eosin staining. The mRNA and protein products of HIF 1α and iNOS were detected by in situ hybridization and immunohistochemistry, respectively Result After 7 days of hypoxia, mPAP rose and HPSR appeared, and the right ventricular hypertrophy was found after 14 days of hypoxia In the control rats, iNOS,iNOSmRNAand HIF 1αmRNA were meakly positivein the pulmonary arterial wall, while HIF 1αprotein was negative in pulmonary arterial tunica intimae and weakly positive in tunica media The expression of iNOS and iNOS mRNA in the pulmonary arterial wall was up regulated after 3 days, reached the peak after 7 days of hypoxia, and then remained sfable The expression of HIF 1αmRNA in the pulmonary arterial wall began to increase significantly after hypoxia for 14 days HIF 1αprotein was strongly positive in pulmonary arterial tunica intimae all of the hypoxic rats; whereas in pulmonary arterial tunica media, the expression of HIF 1αprotein was up regulated and reached the peak level after 3 days, but down regulated after 14 days of hypoxia and restored tobaseline. Linear correlation analysis showed but that iNOS protein was positively correlated with mPAP (r=0 74, P <0 01) and HPSR (r=0 78, P <0 01) but is negatively correlated with HIF 1αprotein (r=-0 52, P <0 01) ConclusionBoth HIF 1αand iNOS are involved in the pathogenesis of hypoxic pulmonary hypertension in rats. HIF 1αmay up regulate iNOS by activating its transcription, whlile iNOS may inhibit the expression of HIF 1α更多还原