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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

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第1期
页码:
51-55
栏目:
基础研究
出版日期:
2010-01-04

文章信息/Info

Title:
Effects of bosentan on right ventricular hypertrophy and connexin43 in rats with chronic hypoxic pulmonary hypertension
作者:
刘海莲1; 张玉顺2; 王佳兴1; 朱妙章3
第四军医大学:1.西京医院心内科， 3.生理学教研室， 陕西 西安 710032; 2.西安交通大学医学院第一附属医院心内二科， 陕西 西安 710061
Author(s):
LIU Hai-lian1;  ZHANG Yu-shun2;  WANG Jia-xing1;  ZHU Miao-zhang3
1.Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China; 2.Second Department of Cardiology, First Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China; 3.Depar
关键词:
低氧性肺动脉高压; 波生坦; 心肌肥厚; 缝隙连接蛋白Cx43; 大鼠
Keywords:
hypoxic pulmonary hypertension;  bosentan;  hypertrophy;  connexin43;  rats
分类号:
R541.3
DOI:
-
文献标识码:
A
摘要:
目的: 研究波生坦(bosentan,BST)对慢性低压低氧性肺动脉高压(HPH)大鼠右心室肥厚及缝隙连接蛋白43(Cx43)表达量的影响。方法: 将24只实验动物随机分为正常组、HPH组、安慰剂组和BST治疗组，每组各6只。正常组：常压常氧下饲养6周；其他3组大鼠置于低压低氧仓内8 h/d,共6周，从第4周开始，每天给BST治疗组大鼠BST （100 mg/kg）灌胃，安慰剂组生理盐水灌胃。6周后，所有大鼠测定血流动力学指标：如平均肺动脉压力（mPAP）、右心室收缩压（RVSP）、右心室收缩压上升最大速率（dp/dtmax），以及右心室肥厚度［如右心室质量/（左心室质量+室间隔质量），RV/(LV+S)］和右心室质量/体质量（RW/BW）。收集动脉血检测血浆内皮素-1（ET-1）和一氧化氮（NO）水平。Masson染色观察心肌胶原纤维容积百分比的变化，免疫组化染色法和Western blot观察Cx43的变化。结果: BST治疗组大鼠的mPAP、RVSP、RV/(LV+S)、RW/BW及心肌胶原纤维容积百分比均较HPH组显著降低（P<0.05），但血浆NO、ET-1的水平和心肌Cx43表达量显著升高（P<0.05）。结论: BST在降低肺动脉压力的同时，还可抑制右心室肥厚和Cx43表达量的降低。
Abstract:
AIM: To study the effects of bosentan on right ventricular hypertrophy and connexin43 in rats with chronic hypoxic pulmonary hypertension (HPH). METHODS: Twenty four rats were randomly divided into four groups: control group, bosentan group, placebo group and HPH group. Rats in the control group were in a normal environment for 6 weeks. Rats in the other groups were kept in a hypobaric chamber that simulated the 5 000 m altitude for 8 h/day for 6 weeks. For placebo group and bosentan group, sodium chloride or bosentan was given for 3 weeks starting from the fourth week. At the end of the 6 weeks, pulmonary arterial pressure (PAP) and right ventricular systolic pressure (RVSP) were determined, RV/LV+S and the weight ratio of the right ventricle weight vs. body weight (RW/BW) were calculated. Right ventricle tissues were Masson stained to observe the degree of myocardial fibrosis. Expression of connexin43 was detected by immunohistochemistry and Western blot. Levels of NO and ET-1 in plasma were measured. RESULTS: PAP and RVSP significantly decreased in bosentan group compared with HPH group (P<0.05). The development of the RV/LV+S and RW/BW was significantly prevented in the bosentan group. Masson stain showed that the degree of myocardial fibrosis significantly decreased in bosentan group compared with HPH group (P<0.05). Level of ET-1 and NO in plasma significantly increased in bosentan group compared with that in HPH group (P<0.05). Expression of connexin43 significantly increased in the bosentan group compared with HPH group (P<0.05). CONCLUSION: Bosentan effectively decreases pulmonary artery pressure and restrains right ventricular hypertrophy and remodeling of connexin43.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2009-1-15.通讯作者：张玉顺，教授，主要从事先天性心脏病的介入治疗的研究Email:zys2889@sina.com 作者简介：刘海莲，硕士生Email:liuhailian79@163.com
更新日期/Last Update: 2010-01-05