缺氧诱导因子1α及血管内皮生长因子在新生大鼠缺氧性肺动脉高压发病机制中的作用

摘要

目的 探讨缺氧诱导因子1α(HIF-1α)及血管内皮生长因子(VEGF)在新生大鼠缺氧性肺动脉高压(HPH)发病机制中的作用.方法 将80只Wistar新生大鼠按随机数字表法分为HPH组和对照组各40只,HPH组为低氧诱导的新生大鼠HPH模型.分别于缺氧3、7、14、21 d时检测各组新生大鼠平均肺动脉压(mPAP),用反转录一聚合酶链式反应方法及Western blot方法检测肺组织中HIF-1α、VEGF mRNA及蛋白质表达水平,并进行HIF-1α和VEGF与mPAP的相关性分析.结果 缺氧3、7、14、21 d时HPH组mPAP(mmHg)均高于对照[(8.5±1.5)比(5.2±1.0)、(12.1±2.1)比(9.6±0.8)、(12.9+2.0)比(9.1±0.8)、(21.0±2.3)比(11.2±1.6)],差异有统计学意义(P<0.05);缺氧3、7、14 d时HPH组肺组织HIF-1αmRNA表达水平高于对照组,缺氧7 d时HIF-1α蛋白质表达量高于对照组,缺氧7、14、21 d时,HPH组VEGF mRNA及蛋白质表达水平均明显高于对照组,差异均有统计学意义(P<0.05),缺氧21 d内HPH组HIF-1α蛋白质表达与mPAP变化成正相关(P<0.05),缺氧7、14、2l d时,VEGF蛋白质表达总体与mPAP变化成正相关(P<0.05).结论 HIF-1α和VEGF共同参与了新生大鼠HPH的发生及发展.%Objective To study the roles of hypoxia-inducible factor-l alpha ( HIF-1α ) and vascular endothelial growth factor ( VEGF) in the pathogenesis of hypoxia-induced pulmonary hypertension ( HPH) in neonatal rats. Methods Wistar neonatal rats were assigned into HPH group and the control group using random number table method. Neonatal rats in HPH group were exposed to hypoxia according to HPH model. On day 3 , 7 , 14 and 210f hypoxia,the mean pulmonary artery pressure ( mPAP) , the level of mRNA and protein expression of HIF-1α and VEGF in lung tissue were examined using RT-PCR and Western blot methods respectively. The correlation of HIF-1,VEGF and mPAP were also analyzed. Results The mPAP ( mmHg) in HPH group on day 3 ,7 ,14 and 210f hypoxia were all higher than the control up[8.5±1.5)vs.5.2±1.0),(12.1±2.1)vs.9.6±0.8),(12.9±2.0)vs.(9.1±0.8),(21.0±2. 3) vs. (11. 2 + 1. 6) ,P < 0. 05]. 0n day 3, 7 and 140f hypoxia,the mRNA of HIF-1α in lung tissue of HPH group were significantly higher than the control group ( P < 0. 05 ) . On day 70f hypoxia, the HIF-1αprotein in lung tissue of HPH group was significantly higher than the control group(P < 0. 05 ) . On day 7 ,14 and 210f hypoxia,the mRNA and protein of VEGF in lung tissue of HPH group were also significantly higher than the control group( P < 0. 05 ). Correlation analysis showed that HIF-1α protein were positively correlated with mPAP on day 3 ,7 . 14 and 21 0f hypoxia in HPH group ( r = 0. 504 .P = 0. 002) , and VEGF protein were positively correlated with mPAP in HPH group on day 7 , 14 and 21 0f hypoxia( r = 0. 782, P < 0. 001) .Conclusion Both HIF-1α and VEGF play roles in the occurrence and development of HPH in neonatal rats.