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波生坦对实验性高原性肺动脉高压的逆转作用(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第4期
页码:
488-492
栏目:
基础研究
出版日期:
2009-06-25

文章信息/Info

Title:
Bosentan in reversal of chronic high-altitude environmentally induced pulmonary hypertension in rats
作者:
王佳兴1; 张玉顺1; 2; 刘海莲1; 朱妙章3
第四军医大学:1.西京医院心内科，3.基础部生理学教研室，陕西 西安 710032； 2.西安交通大学第一附属医院心内二科，陕西 西安 710061
Author(s):
WANG Jia-xing1;  ZHANG Yu-shun1; 2;  LIU Hai-lian1;  ZHU Miao-zhang3
1.Department of Cardiology, Xijing Hospital, 3.Department of Physiology, School of Basic Medicine, Fourth Military Medical University, Xian 710032, Shaanxi, China; 2.Second Department of Cardiology, First Affiliated Hospital, Medical College, Xian Jiaotong University, Xian 710061, Shaanxi, China
关键词:
肺动脉高压; 高原性; 波生坦; 内皮素; 一氧化氮
Keywords:
pulmonary hypertension;  high altitude;  bosentan;  endothelin;  nitric oxide
分类号:
R541. 4
DOI:
-
文献标识码:
A
摘要:
目的 研究波生坦对实验性高原性肺动脉高压大鼠的逆转作用。方法 雄性SD大鼠随机分为5组：正常组，低压低氧3周组，，低压低氧6周组，安慰剂组和波生坦组。除正常组外，其它组置于模拟海拔5 000 m高原的减压舱中，8 h/d，分别持续3周，6周。自4周起，安慰剂组和波生坦组大鼠在低压低氧前分别给予生理盐水或波生坦灌胃。测定各组大鼠的肺血流动力学变化、右心室肥厚指数、肺系数；光镜观察直径小于100 μm肺动脉管壁厚度百分比和40~60 μm肺动脉的肌化度；分别测定血浆和肺组织中内皮素-1（ET-1）、一氧化氮（NO）的含量，肺组织中一氧化氮合酶（NOS）活性。结果 波生坦显著降低了高原性PH大鼠的肺动脉压和右心室收缩压，逆转了肺动脉的重构。波生坦减少了肺组织中的ET-1的含量，增加肺组织中结构性NOS(cNOS)和总NOS的活力，升高了血浆和肺组织中NO的水平。结论 波生坦可逆转已形成的高原性肺动脉高压，其机制可能与降低肺组织中ET-1的含量、增加机体内cNOS和总NOS的活性、升高体内NO的水平有关。波生坦对高原性肺动脉高压有积极的治疗意义。
Abstract:
AIM: To investigate the role of bosentan in the reversal of chronic high-altitude environmentally induced pulmonary hypertension in rats. METHODS: Fifty Male Sprague Dawley rats were randomly divided into five groups: control group, 3-week hypobaric hypoxic group (3 weeks), 6-week hypobaric hypoxic group (6 weeks), placebo group, and bosentan group. Rats in the control group were housed in an orthobaric environment. Rats in the experimental altitude groups were kept in a hypobaric chamber, which simulated the environment of a 5 000 m altitude for 8 h/d. In placebo group and bosentan group, the 3-week administration of sodium chloride or bosentan in hypobaric chamber commenced 3 weeks after hypobaric hypoxic environment. At the end of 3 weeks and 6 weeks, pulmonary arterial pressure (PAP) and right ventricular systolic pressure (RVSP) were recorded, and RV/(LV+S)% and the weight ratio of lung weight vs. body weight: (PW/BW)‰ were calculated. The lung tissues were stained with H/E. Morphometric parameters ［percentage of vascular wall thickness (WT%) and muscularization of non-muscularited peripheral pulmonary arterioles］ were used to assess the remodeling of small pulmonary arteries. The levels of NO and ET-1 in plasma and tissue and the activity of cNOS and total NOS in tissue were measured. RESULTS: PAP and RVSP significantly decreased in bosentan group compared with those in the 3-week group (P<0.05). The development of RV/(LV+S)% and (PW/BW)‰ were significantly inhibited in the bosentan group. Histological study showed that WT% and muscularization of non-muscularized peripheral pulmonary arterioles significantly decreased in the bosentan group compared with those in the 3-week group (P<0.05). The level of ET-1 in the lung homogenates significantly decreased in the bosentan group compared with that in the placebo group (P<0.05). The level of NO and the activity of cNOS and total NOS significantly increased in the bosentan group compared with placebo group (P<0.05). CONCLUSION: Bosentan effectively reverses the development of pulmonary hypertension, reduces the pulmonary vascular remodeling and prevents pulmonary edema in chronic high-altitude environmentally induced pulmonary hypertension in rats. The therapeutic effect of bosentan on chronic high-altitude environmentally induced pulmonary hypertension in rats may result from the decrease of ET-1 in lung and the increase of NO and cNOS in lung and plasma.

参考文献/References

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［12］栾丽丽,李志超,黄玉芳,等. NO及NOS在低氧大鼠肺组织和主动脉中的差异性及其意义［J］. 心脏杂志, 2007, 19(3):258-261.

备注/Memo

备注/Memo:
收稿日期：2008-10-30.通讯作者：张玉顺，教授，主要从事心脏病研究Email:zys2889@sina.com 作者简介：王佳兴，硕士生Email:rumeng@fmmu.edu.cn
更新日期/Last Update: 2009-06-15