中文摘要：

目的 探讨Siah1对大鼠低氧性肺动脉高压（HPH）发病的调控机制.方法 40只成年雄性Wistar大鼠按随机数字表法随机分为对照组和低氧3、7、14、21 d组,每组8只,常压间断低氧复制HPH大鼠模型,对照组大鼠常氧下饲养.测各组大鼠平均肺动脉压（mPAP）、右室肥厚指数（RVHI）、管壁面积与血管总面积比值（WA％）、管腔面积与血管总面积比值（LA％）;原位杂交检测肺内低氧诱导因子1α（HIF-1α）、血管内皮生长因子（VEGF） mRNA相对表达量,免疫组化检测其蛋白质相对表达量;原位杂交、逆转录-PCR检测肺内低氧诱导因子抑制因子（FIH）、Siah1 mRNA相对表达量,免疫组化、Western印迹法检测其蛋白质相对表达量.结果 低氧7d组mPAP、WA％、LA％显著高于对照组[（21.3±1.6） mmHg比（15.9 ±1.3）mmHg（1 mmHg =0.133 kPa）、（41.4±2.8）％比（35.0±2.2）％、（58.6±2.8）％比（65.0±2.2）％,均P＜0.05],低氧14 d组达高水平并维持.低氧14d组RVHI显著高于对照组[（27.0±1.8）％比（23.2±2.1）％,P＜0.05].低氧14 d组HIF-1αmRNA相对表达量显著高于对照组[（0.188 ±0.014）比（0.150 ±0.014）,P＜0.05];低氧3d组HIF-1α蛋白相对表达量显著高于对照组（0.186±0.014比0.067±0.008,P＜0.05）.低氧7d组VEGFmRNA、蛋白相对表达量显著高于对照组（0.152±0.019比0.057±0.007、0.176±0.017比0.083±0.010,均P＜0.05）.FIH mRNA表达在低氧后无显著变化,低氧7d组FIH蛋白相对表达量显著低于对照组（0.166 ±0.015比0.200 ±0.017,P＜0.05）.低氧7d组Siah1 mRNA、蛋白表达均显著高于对照组（0.144 ±0.014比0.067 ±0.010、0.136±0.017比0.084±0.019,均P＜0.05）.HIF-1α蛋白与VEGF mRNA、VEGF蛋白表达均呈正相关（r=0.545、0.523,均P＜0.01）;FIH蛋白与VEGFmRNA、VEGF蛋白表达均呈负相关（r=-0.785、-0.788,均P＜0.01）;Siah1 mRNA与Siah1蛋白表达呈正相关（r =0.823,P＜0.01）;Siah1蛋白与FIH蛋白表达呈?

英文摘要：

Objective To explore the regulatory mechanism of Siah1 in the pathogenesis of hypoxic pulmonary hypertension （HPH） in rats.Methods According to the random number table,40 adult male Wistar rats were randomly divided into 5 groups （n =8 each）.And the animals were exposed to normoxia or hypoxia for 3,7,14 or 21 days respectively.The HPH model was established by normobaric intermittent hypoxia.Mean pulmonary arterial pressure （mPAP）,ratio of vascular wall area to total vascular area （WA%）,ratio of vascular lumen area to total vascular area （LA%） and right ventricle hypertrophy index （RVHI） were measured.The mRNA and protein relative levels of hypoxia-inducible factor-1 α （HIF-1α） and vascular endothelial growth factor （VEGF） were detected by in situ hybridization and immunohistochemistry respectively.Reverse transcriptase-polymerase chain reaction （RT-PCR） and in situ hybridization were used to determine the relative expressions of mRNA of hypoxia-inducible factor-1 （FIH） and Siah1.Immunohistochemistry and Western blot were employed to determine the relative expressions of proteins of FIH and Siah1.Results The levels of mPAP,WA% and LA% were significantly higher after 7-day hypoxia than those in normoxic control （（21.3 ± 1.6） vs （15.9 ± 1.3） mmHg （1 mmHg =0.133 kPa）,（41.4±2.8）% vs （35.0±2.2）%,（58.6±2.8）% vs （65.0±2.2）%,all P〈0.05）.The level of RVHI was significantly higher after 14-day hypoxia than that in normoxic control （（27.0 ± 1.8） % vs （3.2 ±2.1） %,P 〈0.05）.The relative expression of HIF-1α mRNA was significantly higher after 14-day hypoxia than that in normoxic control （0.188 ± 0.014 vs 0.150 ± 0.014,P 〈 0.05）.The relative expression of HIF-1o protein was significantly higher after 3-day hypoxia than that in normoxic control （0.186±0.014 vs 0.067 ± 0.008,P 〈 0.05）.The relative levels of VEGF mRNA and protein were significantly higher after 7-day hypoxia than those in normoxic control （0.152 ±