缺氧性肺动脉高压大鼠泡内肺动脉与右心室胶原表达及黄芪的干预作用

Collagen expression of intra acinar pulmonary arteries and right ventricle and intervention of Radix Astragali in rats with hypoxic pulmonary hypertension

目的 观察缺氧性肺动脉高压大鼠泡内肺动脉与右心室胶原表达及黄芪的干预作用 ,初步探讨其作用机制。方法 将雄性Wistar大鼠随机分为 3组 :( 1)缺氧组 :在常压缺氧舱内缺氧 ,每日 12小时 ,连续 3周 ;( 2 )黄芪组 :缺氧条件同缺氧组 ,自缺氧第一天起给大鼠每天腹腔注射 0 2ml黄芪注射液 ;( 3 )正常对照组 :室内空气正常饲养。用心导管和Fick’s法测定肺动脉压和右心排血量 ,苦味酸天狼猩红染色切片观察泡内肺动脉胶原表达 ,逆转录聚合酶链反应 (RT PCR)检测右心室胶原mRNA、肺组织内皮素 1(ET 1)和一氧化氮合酶 (NOS)mRNA的表达。结果 ( 1)与正常对照组比较 ,缺氧组肺动脉压明显升高 [( 2 4 8± 3 6)mmHg,( 18 8± 1 7)mmHgP <0 0 1],泡内肺动脉胶原表达明显增多 [( 2 0 4± 4 5 )AU ,( 3 4± 1 1)AUP <0 0 1],右心室I型胶原mRNA表达增高 ,肺组织中ET 1mRNA表达增加 ,而NOSmRNA表达下降 ;( 2 )与缺氧组比较 ,黄芪组右心排血量明显升高 (分别为 14 1± 2 0 )ml/min ,( 118± 4 0 )ml/min (P <0 0 1) ,泡内肺动脉胶原表达明显减少 (分别为 5 6± 1 2 )AU ,( 2 0 4± 4 5 )AU (P <0 0 0 1) ,右心室I型胶原的mRNA表达明显下降 ,肺组织中ET 1mRNA表达明显下降 ,而NOS的mRNA表达升高。结论 ?

Objective To investigate the collagen expression effect of intra acinar pulmonary arteries and the right ventricle and to observe the intervention effect of Radix Astragali in rats with hypoxic pulmonary hypertension Methods Wistar male rats were divided into three groups: hypoxia group, which was fed in hypoxic environment (oxygen concentration was 9%～12%) under normal atmospheric pressure for three weeks (12 hours every day); intervention group, which was abdomenly injected with Radix Astragali and fed in the same environment as hypoxia group; and control group, which was fed in normal environment Pulmonary artery pressure and cardiac output of the right ventricle were measured with catheterization and Fick's method Protein expression of collagen in intra acinar pulmonary arteries was assessed with histopathologic method mRNA expressions of collagen in the right ventricle, and endothelin 1 and nitric oxide synthase in lung tissue were evaluated by RT PCR technique Results Compared with those in control group, pulmonary artery pressure and protein expression of collagen in intra acinar pulmonary arteries and mRNA expression of typeⅠcollagen in the right ventricle and endothelin 1 in lung tissue were obviously increased in hypoxia group (mean pulmonary artery pressure: (24 8±3 6) mm Hg vs (18 8±1 7) mm Hg, P <0 01; protein expression of collagen: (20 4±4 5) AU vs (3 4±1 1) AU ( P <0 01), but mRNA expression of nitric oxide synthase in lung tissue was declined Compared with the data obtained in hypoxia group, cardiac output and mRNA expression of nitric oxide synthase in lung tissue were raised in intervention group (cardiac output: [(141±20) ml/min vs (118±40) ml/min, P <0 01], but protein expression of collagen in intra acinar pulmonary arteries and mRNA expression of typeⅠcollagen in the right ventricle and endothelin 1 in lung tissue were markedly decreased (protein expression of collagen: [(5 6±1 2) AU vs (20 4±4 5) AU, P <0 001] Conclusion Changes of collagen expression in intra acinar pulmonary arteries and right ventricle are one of the most important features in remodeling of pulmonary arteries and right ventricle in hypoxic pulmonary hypertension Radix Astragali can partly inhibit the remodeling of pulmonary arteries and right ventricle, and regulate mRNA expression of endothelin 1, nitric oxide synthase, and collagen, thus contributing to the treatment of hypoxic pulmonary hypertension