安立生坦对低氧性肺动脉高压大鼠肺血管平滑肌细胞增殖与凋亡的影响  

The effect of ambrisentan on proliferation and apoptosis of pulmonary vascular smooth muscle cell in rats with hypoxic pulmonary hypertension

作　　者：宋强 胡志 王军[1] 范粉灵[1] 王宇星 张玉顺[1] SONG Qiang;HU Zhi;WANG Jun;FAN Fen-ling;WANG Yu-xing;ZHANG Yu-shun(Department of Structural Heart Disease,The First Affiliated Hospital,Xian Jiaotong University,Xian 710061,China;Electrocardiogram Room,Shaanxi Provincial People s Hospital,Xian 710061,China)

机构地区：[1]西安交通大学第一附属医院结构性心脏病科,陕西西安710061 [2]陕西省人民医院,陕西西安710061

出　　处：《实用医院临床杂志》2018年第6期4-8,共5页Practical Journal of Clinical Medicine

基　　金：国家十二五科技支撑项目(编号:2006BAI01A07)

摘　　要：目的探讨安立生坦对低氧性肺动脉高压大鼠模型肺血管重塑的作用及其内在的分子机制。方法 40只健康SD大鼠采用区组随机化分组方法分为模型组、药物治疗组、安慰剂组及对照组各10只。其中模型组、药物治疗组、安慰剂组大鼠置于低氧舱中饲养。第3周起药物治疗组大鼠进舱前给予安立生坦5 mg/kg灌胃,安慰剂组大鼠于给予生理盐水2 ml灌胃;对照组则置于正常环境中饲养4周。4周后测定各组平均肺动脉压力(m PAP)、右心室收缩压(RVSP);观察肺血管形态学变化,检测右心肥厚指数RV/(LV+S)、管壁厚度占外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%);检测肺血管中Bcl-2、Caspase-3的表达。结果 1.模型组大鼠m PAP和RVSP明显高于对照组(P <0. 05);而药物治疗组组较模型组及安慰剂组显著降低(P <0. 05),与对照组相比无统计学差异(P> 0. 05)。2.与对照组相比,模型组和安慰剂组肺动脉中Bcl-2表达显著升高(P <0. 05);而与模型组、安慰剂组相比,药物治疗组Bcl-2蛋白表达均降低(P <0. 05)。相反,与对照组相比,模型组、安慰剂组Caspase-3表达明显降低(P <0. 05);与模型组、安慰剂组相比,药物治疗组升高(P <0. 05)。结论安立生坦可能通过抑制对动物模型肺动脉平滑肌细胞中Bcl-2的表达,促进Caspase-3的表达,有效降低低氧性肺高压大鼠模型肺动脉压力,有效逆转肺血管重塑。To investigate the role of ambrisentan in lung vascular remodeling in rat model of hypoxic pulmonary hypertension and its underlying mechanism.Forty healthy SD rats were randomized divided into model,drug treatment,placebo and control groups,10 animals in each group.The model group,the drug treatment group and the placebo group were kept in the hypoxia cabin.At the third week,the drug treatment group was given intragastric administration of ambrisentan 5 mg/kg before entering the cabin.The placebo group was given intragastric administration of 2 ml normal saline.The control group was kept in normal environment for 4 weeks.The right ventricular pressure(RVSP)and mean pulmonary arterial pressure(MPA)were determined.The left ventricular+septel(LV+S)and right ventricular hypertrophy index RV/(LV+S)were calculated.The percentage of wall thickness to blood vessel external diameter(WT%)and percentage of wall area to total vascular area(WA%)were calculated.Pulmonary vascular Bcl-2 and caspase-3 in pulmonary artery were detected.1).The MPA and RVSP in the model group were significantly higher than those in the control group(P<0.05)while the indexes in the drug treatment group were significantly lower than those in the model and placebo groups(P<0.05)but not significantly different from the control group(P>0.05).2).Compared with the control group,the expression of Bcl-2 in the model group and the placebo group were significantly increased(P<0.05)while the expression of Bcl-2 protein in the drug treatment group were decreased when compared with the model and placebo groups(P<0.05).In contrast,compared with the control group,the expression of caspase-3 in the model and placebo groups was decreased significantly(P<0.05).Compared with the model group and the placebo group,protein expression of caspase-3 in the drug treatment group was increased(P<0.05).Ambrisentan can effectively reduce the pulmonary artery pressure in hypoxia-induced pulmonary hypertension in rat,and reverse the pulmonary vascular remodeling.The mechanisms mi

关 键 词：低氧性肺动脉高压 安立生坦 肺血管重构 平滑肌增殖 

分 类 号：R543.2[医药卫生—心血管疾病]