中文摘要：

目的：观察缺氧性肺动脉高压（HPH）大鼠肺组织中蛋白激酶B（AKT））和缺氧诱导因子1α（HIF-1α）以及血管内皮生长因子（VEGF）的表达，探讨磷酸肌醇3-激酶（PDK）通路与HIF-1α和VEGF的关系及其在HPH发病中的可能机制。方法：40只成年雄性Wistar大鼠随机分成对照组、低氧3、7、14和21d组，每组8只，测各组大鼠平均肺动脉压（mPAP）、右室肥大指数（RVHI）、血管形态学指标Western印迹检测磷酸化AKT（P—AKT）；原位杂交和免疫组化检测HIF-1α的表达。免疫组化检测P—AKT和VEGF水平。结果：①低氧7d起大鼠mPAP、管壁厚度与血管外径比值及管壁面积与血管面积比值分别为（23．53±1．78）mmHg，（45．5±3．1）％和（54．7±3．2）％，与对照组[（16．15±1．97）mmHg、（36．8±2．5）％、（63．2±2．5）％]比较差异显著（P〈0．05），低氧14d起稳定于高水平；低氧14d RVHI为（26．5±2．9）％，与对照组[（22．9±2．2）％]比较差异也显著（P〈0．05）。②p—AKT蛋白在对照组表达不明显，缺氧3d后表达上升，与对照组比较差异显著（P〈0．05），且在缺氧3d、7d、14d、21d组肺小动脉内膜、中膜表达均为阳性。③HIF-1α蛋白对照组表达不明显，缺氧3d、7d、14d、21d组肺血管内膜均为阳性，肺血管中膜，缺氧3d组表达开始升高（0．209±0．009），与对照组比较差异显著（P〈0．05），缺氧7d达高峰（0．232±0．008，P〈0．05），14d和21d下降；HIF-1α mRNA在对照组肺动脉血管壁内表达弱阳性，缺氧3d和7d肺血管中表达无明显变化，与对照组比较差异无显著（P〉0．05）。缺氧14d后表达增高（0．305±0．104，P〈0．05）．并持续维持于高水平。VEGF蛋白水平在低氧7d显著高于对照组（0．188±0．018，P〈0．05），14d达高峰（0．238±0．017，P〈0．05）。相关分析表明mPAP与肺血管重塑呈正相关（r=0．9

英文摘要：

AIM： To investigate relationship among phosphatidylinositol 3 - kinase （ PI3K） and hypoxia - inducible factor 1α （ HIF - 1α） and vascular endothelial growth factor （VEGF） in lung of rats with hypoxia - inducible pulmonary hypertension. METHODS： Forty male adult Wistar rats were randomly divided into five groups （eight rats in each group） ： control group （C group） and groups with hypoxia for 3, 7, 14 and 21 days （H3, H7 , H14 and H21 group）. Mean pulmonary arterial pressure （mPAP）, right ventric hypertrophy index （RVHI） and vessel morphometry were measured. The levels of HIF - 1α mRNA expression in lung tissue was measured by in siteu hybridization （ISH）. The protein expression of HIF- 1α,VEGF and phosphorylated protein kinase β （P -AKT） were observed by immunohistochemistry or Western blotting. RESULTS： mPAP increased significantly 7 days after hypoxia [ （23.53 ± 1.78） mmHg], peaked 14 days after hypoxia, then remained on the high level. Pulmonary artery remodeling index （extern diameter 100 μm） and RVIH became evident 14 days after hypoxia. Expression of P - AKT protein in control group was poorly positive, but was up - regulated in pulmonary arterial tunica intima and tunica media in all hypoxia rats. HIF - 1α mRNA staining was poorly positive in control, hypoxia for 3 days and hypoxia for 7 days, but began to increase significantly 14 days after hypoxia （0. 305 ±0. 104, P 〈 0.05 ） , then remained stable. Expression of HIF -1α protein in control group was poorly positive, but was up - regulated in pulmonary arterial tunica intima in all hypoxic rats. In pulmonary arterial tunica media, the levels of HIF - 1α protein was markedly up - regulated after 3 days （0. 029 ± 0. 019, P 〈 0. 05 ）, reached its peak 7 days after hypoxia （ 0. 232 ± 0. 008, P 〈0. 05 ） , then tended to decline 14 days and 21 days after hypoxia. Expression of VEGF protein began to increase 7 days after hypoxia （0. 188 ± 0. 018, P 〈 0. 05 ）, reached it