宋强, 张玉顺, 徐晶, 朱妙章. 安立生坦与波生坦对低氧性肺动脉高压大鼠肺血管重构的比较研究[J]. 心脏杂志, 2013, 25(3): 262-266. DOI: 10.13191/j.chj.2013.03.16.songq.007
    引用本文: 宋强, 张玉顺, 徐晶, 朱妙章. 安立生坦与波生坦对低氧性肺动脉高压大鼠肺血管重构的比较研究[J]. 心脏杂志, 2013, 25(3): 262-266. DOI: 10.13191/j.chj.2013.03.16.songq.007
    SONG Qiang, ZHANG Yu-shun, XU Jing, ZHU Miao-zhang. Effect of ambrisentan and bosentan on pulmonary vascular remodeling in rats with hypoxic pulmonary hypertension[J]. Chinese Heart Journal, 2013, 25(3): 262-266. DOI: 10.13191/j.chj.2013.03.16.songq.007
    Citation: SONG Qiang, ZHANG Yu-shun, XU Jing, ZHU Miao-zhang. Effect of ambrisentan and bosentan on pulmonary vascular remodeling in rats with hypoxic pulmonary hypertension[J]. Chinese Heart Journal, 2013, 25(3): 262-266. DOI: 10.13191/j.chj.2013.03.16.songq.007

    安立生坦与波生坦对低氧性肺动脉高压大鼠肺血管重构的比较研究

    Effect of ambrisentan and bosentan on pulmonary vascular remodeling in rats with hypoxic pulmonary hypertension

    • 摘要: 目的:比较安立生坦和波生坦对低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)大鼠肺血管重构治疗效果的比较。方法:40只SD大鼠随机分成5组:对照组、模型组、波生坦组、安立生坦组和安慰剂组,每组8只。对照组于自然环境中饲养4周,其他组置于低压低氧舱中低氧(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)、波生坦组(125 mg/kg)和生理盐水(2 ml)灌胃,共两周。实验结束后,测定所有大鼠平均肺动脉压力(mPAP)、右心室收缩末压(RVSP)和右心室压力最大上升速率(dP/dtmax)。各组大鼠肺组织以HE染色后,观察中小动脉形态的变化。应用图像分析系统检测管壁厚度占外径的百分比WT(%)和管壁面积占总面积的百分比WA(%)。应用免疫组化染色法检测肺血管平滑肌肌动蛋白(α-SMA)的表达。结果:HE染色切片显示,模型组和安慰剂组大鼠的肺小动脉管壁增厚、管腔狭窄,安立生坦组和波生坦组可基本恢复至对照组状态。与对照组相比,模型组和安慰剂组mPAP、WT(%)、WA(%)和α-SMA蛋白的表达均显著升高(P<0.05),安立生坦组和波生坦组上述各项指标差异均无统计学意义。结论:安立生坦与波生坦均能显著降低HPH大鼠的肺动脉压力,逆转肺血管重构。安立生坦组与波生坦组的治疗效果无统计学差异。

       

      Abstract: AIM: To study the effect of ambrisentan and bosentan on pulmonary vascular remodeling in rats with hypoxic pulmonary hypertension(HPH) and to compare the effect of the two drugs.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 a normal environment for 4 weeks and rats in other groups were kept under hypobaric hypoxia environment(8 h/day) for 4 weeks.For placebo group,ambrisentan group and bosentan group,sodium choride(2 ml),ambrisentan(5 mg/kg) and bosentan(125 mg/kg) were given,respectively,during the third week.After 4 weeks,mean pulmonary arterial pressure(mPAP) and right ventricular systoic pressure(RVSP) were measured.Indexes of wall thickness of pulmonary arterioles including the percentage of vascular wall thickness/vascular external diameter(WT%) and the percentage of vascular wall area/total vascular area(WA%) were determined by a computerized image analyzer.α-SMA protein expression in pulmonary arteriole was observed by immunohistochemistry.RESULTS: H/E staining revealed that the pulmonary vessel wall was thickened and the vessel lumina decreased in the model and placebo groups.Ambrisentan and bosentan reversed this change.Compared with those in the control group,mPAP,WT%,WA% and protein expression of α-SMA increased significantly in the model and placebo groups.No significant difference was observed in the expression of α-SMA and indexes between ambrisentan group and bosentan group.CONCLUSION: Ambrisentan and bosentan significantly decrease pulmonary artery pressure and reverse pulmonary vessel remodeling in rats with HPH.No significant difference has been found in the curative effect between ambrisentan and bosentan.

       

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