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  

Effects of bosentan on right ventricular hypertrophy and connexin 43 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] 

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

出　　处：《心脏杂志》2010年第1期51-55,共5页Chinese Heart Journal

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8h/d,共6周,从第4周开始,每天给BST治疗组大鼠BST(100mg/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Westernblot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。AIM： To study the effects of bosentan on right ventricular hypertrophy and connexin43 in rats with chronic hypoxie 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 ventrieular systolic pressure （RVSP） were determined, RV/IN ＋ S and the weight ratio of the right ventrMe weight vs. body weight （RW/BW） were calculated. Right ventricle tissues were Masson stained to observe the degree of myocardial fibrosis. Expression of cnnnexin43 was detected by immunohistoehemistry 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.

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 

分 类 号：R541.3[医药卫生—心血管疾病]