磷酸肌醇3-激酶在大鼠缺氧性肺动脉高压中的作用

目的：通过观察缺氧性肺动脉高压（HPH）大鼠肺组织中蛋白激酶B（AKT））和血管内皮生长因子（VEGF）的表达,研究磷酸肌醇3-激酶（PI3K）通路与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、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;免疫组化检测P-AKT和VEGF。结果：低氧7d后,mPAP开始上升[（23.53±1.78）mmHg],与对照组比较差异有显著性（P〈0.05）,低氧14d后达高水平并维持于此水平。肺血管重塑,RVIH改变在缺氧14d后出现。磷酸化AKT蛋白在对照组表达不明显,在低氧3d后表达上升,与对照组比较差异有显著性（P〈0.05）,且在低氧3、7、14、21d组肺血管内膜、中膜中,磷酸化AKT蛋白表达均为阳性。VEGF在低氧7d增高（0.188±0.018,P〈0.05）,14d达高峰（0.238±0.017,P〈0.05）。相关分析表明磷酸化AKT、VEGF蛋白、mPAP与血管重塑均正相关（P〈0.01）。磷酸化AKT与VEGF（内膜）成正相关（P〈0.01）。结论：磷酸化AKT与VEGF均在大鼠HPH的发病机制中发挥作用。

Role of Phosphati Dylinositol 3 - kinase of Rats Hypoxia-inducible Pulmonary Hypertension

Objective：To investigate the expression and relationship levels of Phosphatidylinositol 3-kinase（PI3K） and vascular endothelial growth factor（VEGF） in lung of rats with Hypoxia-inducible pulmonary Hypertension.Methods：Forty male adult Wistar rats were randomly devided into five groups：a control group（C group） and Groups with hypoxia for 3,7,14 and 21 days（H3,H7,H14 and H21 group）,eight rats per group.Mean pulmonary pressure（mPAP）,right ventric hypertrophy index（RVHI） and vessel morphometry were measured.,VEGF and P-AKT were observed by immunohistochemistry or western blot.Results：mPAP increased significantly after 7-day of hypoxia [（23.53 ±1.78） mmHg],reach its peak after 14-day of hypoxia,then remain on the high level.pulmonary artery remoldeling index（extern diameter 100μ） and RVIH became evidence after 14-day of hypoxia.expression of P-AKT protein in control group was poorly positive,but was up-regulated in pulmonary arterial tunica intima and tunica media ofall hypoxia rats.Expression of VEGF protein began to increase after 7-day of hypoxia（0.188 ± 0.018,P 0.05）,reaching its peak after 14-day of hypoxia（0.238 ± 0.017,P 0.05）,then remained on the high level1 in pulmonary arterial tunica intima.Linear correlation analysis showed that P-AKT,VEGF and mPAP were correlated with vessel morphometry and RVHI（P 0.01）,P-AKT was positively correlated with VEGF（tunica intima）.Conclusions：p AKT and VEGF are all involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats.