安立生坦与波生坦对低氧性肺动脉高压大鼠右心室重构影响的比较研究  

Comparative study of the effects of ambrisentan and bosentan on right ventricle remodeling in rats with hypoxic pulmonary hypertension

作　　者：徐晶[1] 张玉顺[1] 宋强[1] 朱妙章[2] 

机构地区：[1]西安交通大学医学院第一附属医院心内二科,陕西西安710061 [2]第四军医大学基础部生理学教研室,陕西西安710032

出　　处：《心脏杂志》2013年第3期257-261,共5页Chinese Heart Journal

摘　　要：目的:比较安立生坦(ambrisentan)与波生坦(bosentan)对低氧性肺动脉高压大鼠(HPH)右心室重构的影响。方法:40只SD大鼠随机分成5组:正常对照组、模型组、安立生坦组、波生坦组、安慰剂组,每组8只。正常对照组于自然环境中饲养4周,其他组置于低压低氧舱中(8 h/d)饲养4周。从低氧开始第3周起,安立生坦组、波生坦组和安慰剂组大鼠每天进舱前依次分别给予安立生坦(5 mg/kg)、波生坦(125 mg/kg)及生理盐水(2 ml)灌胃,共两周。实验结束后,测定平均肺动脉压(mPAP)和右心室收缩压(RVSP);计算右心室肥厚指数[RV/(LV+S)]及右心室质量/体质量(RW/BW)。右心室心肌以HE染色后,观察其形态学变化,以Masson染色后观察心肌胶原纤维容积分数(CVF)的变化。结果:与模型组和安慰剂组相比,安立生坦组和波生坦组的mPAP、RVSP、RV/(LV+S)、RW/BW、CVF值明显降低(P<0.05),安立生坦组和波生坦组相比,上述指标的差异无明显的统计学意义。HE染色切片显示,模型组和安慰剂组大鼠心肌细胞肥大,安立生坦组和波生坦组可基本恢复至正常组状态。结论:安立生坦与波生坦能显著降低HPH大鼠的肺动脉压力,抑制右心室肥厚及纤维化。安立生坦与波生坦相比,对HPH大鼠右心室重构的影响无明显差别。AIM： To compare the effects of ambrisentan and bosentan on right ventricle remodeling in rats with hypoxic pulmonary hypertension（HPH）.METHODS： Forty Sprague Dawley rats were randomly divided into five groups： control group,model group,ambrisentan group,bosentan group and placebo group（eight rats in each group）.Rats in the control group were kept under normal environment for 4 weeks while rats in the other groups were kept in hypobaric hypoxia environment（8 h/day） for 4 weeks.For bosentan group,ambrisentan group and placebo group,bosentan（125 mg/kg）,ambrisentan（5 mg/kg） and normal saline（2 ml） were given at the third week,respectively.At the end of 4 weeks,mean pulmonary arterial pressure（mPAP） and right ventricular systolic pressure（RVSP） were determined.RV/（LV＋S） and the weight ratio of right ventricle weight vs.body weight（RW/BW） were calculated.The right ventricle tissues were Masson stained to observe the degree of myocardial fibrosis and in H/E to observe the pathological changes.RESULTS： Compared with those in the model group and the placebo group,mPAP,RVSP,RV/（LV＋S）,RW/BW and CVF in ambrisentan group and bosentan group were significantly reduced,with no statistically significant difference in the observed indexes between ambrisentan group and bosentan group.H/E staining revealed that the degree of myocardial hypertrophy significantly attenuated in ambrisentan group and bosentan group compared with that in model and placebo groups.CONCLUSION： Ambrisentan and bosentan effectively decreases pulmonary artery pressure and restrains right ventricular hypertrophy and myocardial fibrosis in rats with HPH.There is no significant difference in the effects of ambrisentan and bosentan on right ventricle remodeling in rats with HPH.

关 键 词：低氧性肺动脉高压 安立生坦 波生坦 心肌肥厚 纤维化 

分 类 号：R543.2[医药卫生—心血管疾病]