文章摘要

文章信息/Info

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

作者:: 宋强¹; 张玉顺¹; 徐晶¹; 朱妙章²; (1.西安交通大学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)

Author(s):: SONG Qiang¹; ZHANG Yu shun¹; XU Jing¹; ZHU Miaozhang²; (1.Second Department of Cardiology, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China; 2.Department of Physiology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)

关键词:: 低氧性肺动脉高压; 安立生坦; 波生坦; 肺血管重构

Keywords:: Hypoxic pulmonary hypertension; ambrisentan; bosentan; pulmonary vascular remodeling

分类号:: R543.3

DOI:: -

文献标识码:: A

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 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, with eight rats in each group. The rats in control group were kept under a normal environment for 4 weeks and the rats in other groups were kept in hypobaric hypoxia environment (8 h/d) 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 at 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: HE staining revealed that the pulmonary vessel wall was thickened and the vessel lumina decreased in model group and placebo group. Ambrisentan and bosentan reversed this change. Compared with those in control group, mPAP, WT(%), WA(%) and the protein expression of αSMA increased significantly in model group and placebo group. 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 the pulmonary vessel remodeling in HPH rats. No significant difference has been found in the curative effect between ambrisentan and bosentan.

参考文献/References

[1]Jacobs A,Preston IR,Gomberg Maitland M.Endothel in receptor antagonism in pulmonary arterial hypertension a role for selective ETA inhibition?[J].Curr Med Res Opin,2006,22(12):2567-2574.
[2]Fukumoto Y,Tawara S,Shimokawa H.Recent progress in the treatment of pulmonary arterial hypertension:expectation for rhokinase inhibitors[J].Tohoku J Exp Med,2007,211(4):309-320.
[3]Hewage CM,Jiang L,Parkinson JA,et al.A linear endothelin 1 analogue: solution structure of ET1 ［A ib l, 3, 11, 15, N le 7 ］ by nuclear magnet ic resonance spectroscopy and mo lecular modelling[J].Neurochem Int,1999,35(1):35-45.
[4]刘海莲,张玉顺,王佳兴,等.波生坦对慢性低氧性肺动脉高压大鼠右心室肥厚及缝隙连接蛋白(Cx)43表达的影响[J].心脏杂志,2010,22(1):51-55.
[5]Pei JM,Sun X,Guo HT,et al.U50,488 H Depresses pulmonary pressure in rat subjected to chronic hypoxia[J].J Cardiovasc Pharmacol, 2006, 47(4):594-598.
[6]罗风鸣,刘小箐,王曾礼,等.支气管哮喘大鼠气道重构与平滑肌肌动蛋白a表达的关系[J].中华结核和呼吸杂志,2002,25(12):762-763.
[7]齐建光,杜军保,郭志良.L-精氨酸调节大鼠低氧性肺血管结构重建与肺动脉平滑肌细胞凋亡[J].北京大学学报(医学版),2001,33(4):339-343.
[8]宫丽敏,杜军保,石云.一氧化碳对缺氧大鼠肺动脉平滑肌细胞增殖和凋亡的影响[J].实用儿科临床杂志,2001,16(5):257-259.
[9]Channick RN,Simonneau G,Sitbon O,et al.Effects of the dual endo thelinreceptor antagonist bosentan in patients with pulmonary hypertension:a random ised placebo controlled study[J].Lancet,2001,358(9288):1119-1123.
[10]荆志成.波生坦治疗肺动脉高压的药理机制及其临床评价[J].中国医院用药评价与分析,2005,15(6):334-338.
[11]Davenport AP,Maguire JJ.Is endothelin induced vasoconstriction mediated only by ETA receptors in humans?[J].Trends Pharmacol Sci,1994,15(1):9-11.

我们的网站为什么显示成这样？

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

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

文章信息/Info

参考文献/References

备注/Memo

常用功能

导航/Navigate

工具/Tools

统计/Statistics