大鼠缺氧性肺动脉高压过程中缺氧诱导因子1α和血红素氧合酶1的变化  

Changes of hypoxia inducible factor 1 alpha and heme oxygenase 1 in the process of hypoxic pulmonary hypertension development in rats

作　　者：李启芳[1] 戴爱国 

机构地区：[1]南华大学,湖南衡阳421001 [2]湖南省老年医院

出　　处：《中国病理生理杂志》2005年第7期1260-1264,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30270581);湖南省教育厅重点科研基金(No.02A047);中国博士后科学基金会(No.2003033436)资助

摘　　要：目的:观察缺氧大鼠肺小血管壁缺氧诱导因子1α(HIF-1α)和血红素氧合酶1(HO-1)基因表达。方法:40只雄性Wistar大鼠随机分成缺氧0、3、7、14和21d组。测平均肺动脉压(mPAP),血管形态学指标,右室肥大指数(RVHI),HO-1活性和HIF-1α,HO-1基因表达。结果:缺氧7dmPAP高于对照组,缺氧14d达到高峰并维持于此水平。肺血管重塑,RVHI改变在缺氧14d后出现。HIF-1α蛋白在对照组表达不明显,各缺氧组血管内膜均为阳性。在中膜,HIF-1α蛋白缺氧3d开始增高,第7d达到高峰,14d和21d后下降,HIF-1αmRNA缺氧14d增高,此后维持于高水平。HO-1蛋白在缺氧7d后增高,14d后达到高水平,并持续于高水平。HO-1mRNA缺氧3d增高,7d达高峰,之后下降。结论:HIF-1α和HO-1均在大鼠缺氧性肺动脉高压的发病机制中发挥作用,且HIF-1α与HO-1基因表达可能有相互调控。AIM: To observe the expression of hypoxia inducible factor-1α (HIF-1α) gene and heme oxygenase-1 (HO-1) gene in pulmonary arteries in hypoxic rats. METHODS: Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary pressure (mPAP), vessel morphometry, right ventricle hypertrophy index (RVHI) were measured. Lungs were either inflation fixed for immunohistochemistry and in situ hybridization or frozen for later measurement of HO-1 enzyme activity. RESULTS: During hypoxia, mPAP increased to significantly higher values than the control values after 7-day of hypoxia,reaching its peak after 14-day of hypoxia, then remained on the high level. Pulmonary artery remodeling developed significantly after 14-day of hypoxia. Expression of HIF-1α protein in control was poorly positive, but was up-regulated in pulmonary arterial tunica intimae of all hypoxic rats. In pulmonary arterial tunica media, the levels of HIF-1α protein were markedly up-regulated after 3-day and 7-day of hypoxia, then tended to decline after 14-day and 21-day of hypoxia. HIF-1α mRNA staining was poorly positive in control, hypoxia for 3 days and hypoxia for 7 days, but began to enhance significantly after 14-day of hypoxia, then remained stable. Expression of HO-1 protein began to increase after 7-day of hypoxia, reaching its peak after 14-day of hypoxia, then remained stable. Expression of HO-1 mRNA began to increase after 3-day of hypoxia, reaching its peak after 7-day of hypoxia, then declined. CONCLUSION: HIF-1α and HO-1 are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats. Furthermore, HIF-1α may inter-regulate with HO-1 gene in this process.

关 键 词：缺氧诱导因子-1 血红素氧化酶(脱环) 缺氧 高血压 肺性 基因表达 

分 类 号：R363[医药卫生—病理学]