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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

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第3期
页码:
253-256266
栏目:
出版日期:
2013-06-25

文章信息/Info

Title:
Expression of plateletderived growth factor in pulmonary arteries in rats with highaltitude environmentinduced pulmonary hypertension and its regulation by bosentan
作者:
何 璐1; 张玉顺1; 王佳兴2; 朱妙章3
(1.西安交通大学第一附属医院心血管科，陕西 西安 710061；2.解放军309医院心内科，北京 100091；3.第四军医大学基础部生理学教研室，陕西 西安 710032)
Author(s):
HE Lu1;  ZHANG Yushun1;  WANG Jiaxing2;  ZHU Miaozhang3
(1.Second Department of Cardiology, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China; 2.Department of Cardiology, 309 Hospital of PLA, Beijing 100091, China; 3.Department of Physiology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
高原性肺动脉高压; 波生坦; 血小板源性生长因子; 大鼠
Keywords:
pulmonary hypertension;  high altitude;  bosentan;  plateletderived growth factor;  rat
分类号:
R543.2
DOI:
-
文献标识码:
A
摘要:
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。
Abstract:
AIM:To establish the model of highaltitude environmentinduced pulmonary hypertension rats, 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 rats and on the expression of plateletderived growth factor (PDGF) in pulmonary arterial in rats with highaltitude environmentinduced pulmonary hypertension. METHODS: Rats were exposed to lowpressure and lowoxygen conditions in an auto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. The rats in control group stayed in orthobaric environment while the rats in other groups were kept in hypobaric chamber for 8 hours one 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) were 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 4 groups and the expression of PDGF increased with the increasing time of hypoxia. CONCLUSION: Bosentan successfully reverses the hypoxic pulmonary vascular remodeling, suggesting that bosentan could be used for the treatment of 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.

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备注/Memo

备注/Memo:
收稿日期：2013-03-10.
通讯作者：张玉顺，主任医师，主要从事先天性心脏病介入治疗研究Email:zys2889@sina.com
作者简介：何璐，住院医师，硕士Email：helu926@foxmail.com
更新日期/Last Update: 2013-07-16