缺氧诱导因子1α调控血管内皮生长因子对大鼠缺氧性肺动脉高压的作用  

Hypoxia-inducible factor 1α regulates vascular endothelial growth factor′s roles on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension

作　　者：李启芳[1] 戴爱国 

机构地区：[1]湖南省老年医院,湖南省老年医学研究所呼吸疾病研究室,长沙410001

出　　处：《中华结核和呼吸杂志》2004年第3期174-178,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家自然科学基金资助项目 ( 3 0 2 70 5 81) ;湖南省教育厅重点科研基金 ( 0 2A0 47) ;中国博士后科学基金资助项目 ( 2 0 0 3 0 3 3 43 6)

摘　　要：目的　研究大鼠缺氧性肺动脉高压 (HPH)肺血管壁缺氧诱导因子 1α(HIF 1α)和血管内皮生长因子 (VEGF)基因表达的动态变化。方法　 4 0只成年雄性Wistar大鼠随机分成对照组、缺氧 3、7、14和 2 1d组 ,每组 8只 ,测各组大鼠平均肺动脉压 (mPAP)、血管形态学指标、右室肥大指数(RVHI) ;原位杂交和免疫组化检测HIF 1α,VEGF基因表达。结果　缺氧 7d后 ,mPAP开始上升[(18 4 1± 0 37)mmHg],与对照组比较差异有显著性 (P <0 0 5 ) ,缺氧 14d达高水平并维持于此水平。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 ,各缺氧组肺血管内膜均为阳性 ;在中膜 ,HIF 1α蛋白缺氧 3d始增高 (0 178± 0 0 17) ,与对照组比较差异有显著性 (P <0 0 5 ) ,缺氧 7d达高峰 (0 2 2 1± 0 0 2 1,P <0 0 5 ) ,14d和 2 1d下降 ;HIF 1αmRNA对照组 ,缺氧 3d和 7d组均不明显 ,缺氧 14d增高 (0 2 0 3± 0 0 2 4 ,P <0 0 5 ) ,并维持于高水平。VEGF蛋白在缺氧 7d增高(0 0 74± 0 0 2 2 ,P <0 0 5 ) ,14d达高峰 (0 14 7± 0 0 17,P <0 0 5 )并持续于高水平 ;VEGFmRNA对照组和缺氧 3d组不明显 ,缺氧 7d增高达高峰 (0 138± 0 0 10 ,P <0 0 5 ) ,之后持续于高水平。VEGFmRNA于中膜和内膜。Objective To investigate the dynamic expression of hypoxia inducible factor 1α(HIF 1α) and vascular endothelial growth factor(VEGF) in pulmonary arteries of rats with hypoxia induced pulmonary hypertension Methods Forty male adult Wistar rats were randomly divided into five groups:a control group (C group) and groups with hypoxia for 3,7,14 and 21 days(H 3,H 7,H 14 and H 21 group),eight rats per group Mean pulmonary pressure(mPAP),vessel morphometry and right ventricle hypertrophy index(RVHI) were measured Lungs were inflation fixed for in situ hybridization and immunohistochemistry Results mPAP increased significantly after 7 day of hypoxia [(18 41±0 37) mm Hg, P <0 05],reaching its peak after 14 day of hypoxia,then remained on the high level Pulmonary artery remodeling index(outer diameter 100 150 μm) and RVHI became evident after 14 day of hypoxia Expression of HIF 1α protein in control group was poorly positive,but was up regulated in pulmonary arterial tunica intima of all hypoxic rats In pulmonary arterial tunica media,the levels of HIF 1α protein was markedly up regulated after 3 day(0 178±0 017, P <0 05),reaching its peak after 7 day of hypoxia(0 221±0 021, P <0 05),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 increase significantly after 14 day of hypoxia(0 203±0 024, P <0 05),then remained stable Expression of VEGF protein began to increase after 7 day of hypoxia(0 074±0 022, P <0 05),reaching its peak after 14 day of hypoxia(0 147±0 017, P <0 05),then remained on the high level VEGF mRNA in control and hypoxia for 3 days was poorly positive,but began to increase after 7 day of hypoxia(0 138±0 010, P <0 05),and remained on the high level thereafter VEGF mRNA located mainly in tunica intima and tunica media,whereas VEGF protein located predominantly in tunica intima Linear correlati

关 键 词：缺氧诱导因子1Α 血管内皮生长因子 大鼠 缺氧性肺动脉高压 

分 类 号：R543.2[医药卫生—心血管疾病]