«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2015年第4期

页码:

380-383,396

栏目:

结构性心脏病

出版日期:

2015-04-20

文章信息/Info

Title:

Effects of ambrisentan on osteopontin in rats with hypoxic pulmonary hypertension

作者:

宋渊庆¹; 2; 宋 强³; 徐 晶³; 马 乐³; 张玉顺³

(1.西安交通大学医学部，陕西 西安 710061；
2.西安电力中心医院心肾内科，陕西 西安 710032；
3.西安交通大学第一附属医院心内二科，陕西 西安 710061)

Author(s):

SONG Yuan-qing¹; 2;  SONG Qiang³;  XU Jing³;  MA Yue³;  ZHANG Yu-shun³

(1.Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China；
2.Second Department of Cardiology, Xi’an Electric Central Hospital, Xi’an 710032, Shaanxi, China；
3.Second Department of Cardiology, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China)

关键词:

低氧性肺动脉高压; 安立生坦; 骨桥蛋白

Keywords:

hypoxic pulmonary hypertension;  ambrisentan;  osteopontin

分类号:

R544.1

DOI:

-

文献标识码:

A

摘要:

目的 研究安立生坦（ambrisentan）对低氧性肺动脉高压（hypoxic pulmonary hypertension,HPH）大鼠右心室心肌骨桥蛋白（Osteopontin，OPN）表达的影响。方法 将40只SD大鼠随机分成正常组、模型组、安慰剂组、安立生坦组，每组各10只。正常组于自然环境中饲养4周，其他3组置于低压低氧舱内（8 h/d），共饲养4周。从低氧第3周起进舱前，每天给予安慰剂组生理盐水（2 ml）灌胃，给予安立生坦组安立生坦（5 mg/kg）灌胃，共2周。4周后以RT-PCR及Western blot法检测右心室心肌OPN的表达水平。结果 与正常组相比，模型组大鼠的mPAP、RVSP、RV/(LV+S)、RW/BW、和右心室CVF均显著升高，OPN表达水平显著升高（P<0.05）；与模型组和安慰剂组比较，安立生坦组的上述指标和OPN的表达水平显著降低（P<0.05）；与正常组相比，安立生坦组各项指标及OPN表达水平无明显统计学差异。结论 安立生坦在降低肺动脉压力的同时可显著降低右心室心肌O PN的表达。

Abstract:

AIM To study the effects of ambrisentan on osteopontin in rats with hypoxic pulmonary hypertension. METHODS Forty Sprague Dawley rats were randomly divided into four groups: control group, model group, placebo group and ambrisentan group. Rats in the control group were kept in a normal environment for 4 weeks. Rats in the other groups were kept in a hypobaric chamber for 8 h/day for 4 weeks. For ambrisentan group and placebo group, ambrisentan (5 mg/kg) and normal saline (2 ml) were respectively given at the third week. At the end of 4 weeks, the expression of (osteopontin) OPN in the right ventricle was detected by RT-PCR and Western blot. RESULTS Compared with those in the model group and the placebo group, the expression of OPN in the ambrisentan group was decreased obviously. CONCLUSION Ambrisentan successfully decreases pulmonary artery pressure and restrains the expression of OPN.

参考文献/References

[1]Vonk-Noordegraaf A,Haddad F,Chin KM,et al.Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology[J].J Am Coll Cardiol,2013,62(25 Suppl):D22-D33.
[2]Bogaard HJ,Abe K,Vonk Noordegraaf A,et al.The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension[J].Chest,2009,135(3):794-804.
[3]宋 强,张玉顺,徐 晶,等.安立生坦与波生坦对低氧性肺动脉高压大鼠肺血管重构影响的比较研究[J].心脏杂志,2013,25(3):262-266.
[4]徐 晶,张玉顺,宋 强,等.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[J].心脏杂志,2013,25(3):257-261.
[5]D 'Alto M,Romeo E,Argiento P,et al.Ambrisentan for pulmonary arterial hypertension: long term effects on clinical status, exercise capacity and haemodynamics[J].Int J Cardiol,2012,156(2):244-245.
[6]Kusuyama T,Yoshiyama M,Omura T,et al.Angiotensin blockade inhibits osteopontin expression in non-infarcted myocardium after myocardial infarction[J].J Pharmacol Sci, 2005, 98(3):283-289.
[7]Nagao T,Okura T,Irita J,et al.Osteopontin plays a critical role in interstitial fibrosis but not glomerular sclerosis in diabetic nephropathy[J].Nephron Extra,2012,2(1):87-103.
[8]Zahradka P.Novel role for osteopontin in cardiac fibrosis[J].Circ Res,2008,102(3):270-272.
[9]Yu Q,Vazquez R,Khojeini EV,et al.IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice[J].Am J Physiol Heart Circ Physiol,2009,297(1):H76-H85.
[10]Szalay G,Sauter M,Haberland M,et al.Osteopontin:a fibrosis-related marker molecule in cardiac remodeling of enterovirus myocarditis in the susceptible host[J].Circ Res,2009,104(7):851-859.
[11]Suezawa C,Kusachi S,Murakami T,et al.Time-dependent changes in plasma osteopontin levels in patients with anterior-wall acute myocardial infarction after successful reperfusion: correlation with left-ventricular volume and function[J].J Lab Clin Med,2005,145(1):33-40.
[12]Soejima H,Irie A,Fukunaga T,et al.Osteopontin expression of circulating T cells and plasma osteopontin levels are increased in relation to severity of heart failure[J].Circ J,2007,71(12):1879-1884.
[13]Tousoulis D,Siasos G,Maniatis K,et al.Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease[J].Int J Cardiol,2013,167(5):1924-1928.
[14]Isoda K,Nishikawa K,Kamezawa Y,et al.Osteopontin plays an important role in the development of medial thickening and neointimal formation[J].Circ Res,2002,91(1):77-82.
[15]Xie Z,Singh M,Singh K.Osteopontin modulates myocardial hypertrophy in response to chronic pressure overload in mice[J]. Hypertension,2004,44(6):826-831.
[16]林 全,王良兴 ,罗遐杰,等.低氧和高二氧化碳作用下肺动脉高压形成过程中骨桥蛋白表达与分布的实验研究[J].中国病理生理杂志,2007,23(6):1093-1097.

备注/Memo

备注/Memo:

收稿日期：2015-03-13.
通讯作者：张玉顺，教授，主要从事先天性心脏病介入治疗研究 Email：zys2889@sina.com
作者简介：宋渊庆，硕士生 Email：syq4086@163.com

常用功能

更新日期/Last Update: 2015-04-22