PDGF在高原性肺动脉高压大鼠肺动脉中的表达及波生坦对其表达的影响

Expression of platelet-derived growth factor in pulmonary arteries in rats with high-altitude environment-induced pulmonary hypertension and its regulation by bosentan

目的:观察低氧性肺血管重建(HPSR)中肺动脉平滑肌增生性改变,探讨波生坦(BST)对高原性肺动脉高压(HAEPH)的逆转作用及对HAEPH大鼠肺动脉血小板源性生长因子(PDGF)表达的影响。方法:采用全自动调节的低压低氧舱模拟海拔5 000～5 500 m高度的气压环境(大气压约50 kPa),建立慢性HAEPH大鼠模型。将40只SD大鼠随机分为4组:对照组、模型组、安慰剂组和BST组,每组各10只。对照组常压常氧下饲养6周,其他3组均置于低压低氧仓中进行间断低氧(8 h/d),并分别饲养3周、6周、6周。自第4周起,安慰剂组和BST组大鼠在入仓前分别给予生理盐水(2 ml)和BST(100 mg/kg)灌胃。6周后取肺组织石蜡包埋,连续切片后,观察肺血管形态学变化。用免疫组织化学染色法对各组大鼠肺动脉中PDGF的表达进行定位及半定量分析。结果:①安慰剂组大鼠的肺动脉管壁增厚、管腔狭窄,BST组大鼠的肺动脉管壁厚度及管腔恢复至正常组状态。②各组大鼠肺动脉均有PDGF表达,随低氧时间的延长,PDGF的表达逐渐增加,BST组PDGF的表达与正常组比较无统计学差异。结论:①BST可有效地逆转HPSR,提示BST对HAEPH具有治疗作用。②BST对HAEPH大鼠肺动脉中PDGF的表达具有抑制作用。

AIM： To establish the rat model of high-altitude environment-induced pulmonary hypertension,observe proliferative changes in pulmonary arterial smooth muscle of hypoxic pulmonary vascular remodeling and to explore the effect of bosentan on high-altitude environment-induced pulmonary hypertension in rats and on the expression of platelet-derived growth factor（PDGF） in pulmonary artery in rats with high-altitude environment-induced pulmonary hypertension.METHODS： Rats were exposed to low-pressure and low-oxygen conditions in a self-modulating hypobaric and hypoxic cabin（air pressure 50 kPa,oxygen concentration 10%） to establish the high-altitude environment-induced pulmonary hypertension animal model.Forty male Sprague Dawley rats were randomly divided into four groups： control group,hypoxia group,placebo group and bosentan group.Rats in the control group remained in an orthobaric environment while rats in other groups were kept in hypobaric chamber for 8 h,1 day for 3 weeks,6 weeks and 6 weeks.After 3 weeks＇ exposure to hypobaric hypoxic environment,sodium chloride（2 ml） or bosentan（100 mg/kg） was administrated to placebo group and bosentan group for another 3 weeks.To observe the morphological changes of pulmonary vessels in rats,immunohistochemical technique was used to assess the abundance and localization of platelet-derived growth factor in pulmonary arteries.RESULTS： Thickening and stenosis of pulmonary arteries were observed in placebo group and bosentan reversed the changes.PDGF was expressed in pulmonary arteries in all four groups and the expression of PDGF increased with the increasing time of hypoxia.CONCLUSION： Bosentan successfully reversed hypoxic pulmonary vascular remodeling,suggesting that bosentan may be used to treat high-altitude environment-induced pulmonary hypertension.Bosentan may have a suppressible effect on the expression of PDGF in rats with high-altitude environment-induced pulmonary hypertension.