波生坦对实验性高原性肺动脉高压的逆转作用  

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] 

机构地区：[1]第四军医大学西京医院心内科 [2]西安交通大学第一附属医院心内二科,陕西西安710061 [3]第四军医大学基础部生理学教研室,陕西西安710032

出　　处：《心脏杂志》2009年第4期488-492,共5页Chinese Heart Journal

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5000m高原的减压舱中,8h/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100μm肺动脉管壁厚度百分比和40～60μm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。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 hypoxie group （3 weeks） , 6-week hypobaric hypoxic group （6 weeks） , placebo group, and bosentan group. Rats in the control group were housed in an orthoharic 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）%o were calculated. The lung tissues were stained with H/E. Morphometric parameters [ percentage of vascular wall thickness （WT%） and muscularization of nonmuseularited 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

关 键 词：肺动脉高压 高原性 波生坦 内皮素 一氧化氮 

分 类 号：R541.4[医药卫生—心血管疾病]