COPD肺动脉高压大鼠肺组织血红素氧合酶-1的表达及辛伐他汀治疗对其的影响  

Expression of hemeoxygenase-1 in rats with COPD-induced pulmonary hypertension and the effect of simvastatin on it

作　　者：孙佳玮[1] 李鹏[3] 姜雪[4] 袁林栋 张彬[2] 李珠[1] 孙武装[1] 

机构地区：[1]河北医科大学第一医院呼吸科,石家庄050031 [2]河北医科大学第一医院急诊科,石家庄050031 [3]浙江省苍南县人民医院内科,温州325800 [4]天津市第三中心医院儿科,300170 [5]山东省聊城市人民医院呼吸内科,252000

出　　处：《国际呼吸杂志》2016年第16期1231-1235,共5页International Journal of Respiration

摘　　要：目的 研究辛伐他汀对慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）所致肺动脉高压的作用,以及对肺组织血红素氧合酶-1（Hemeoxygenas-1, HO-1）表达的影响。方法 24只大鼠随机分为三组：对照组、烟雾暴露组和辛伐他汀组。右心导管测定大鼠平均肺动脉压（Mean Pulmonary Arterial pressure, mPAP），以右心室/（左心室＋室间隔）的质量比值（Right Ventricular Hypertrophy Index，RVHI）作为评价右心室肥厚的指标。Real time RT-PCR方法测定肺组织HO-1mRNA的表达，通过免疫印迹法（Western blot）及免疫组化方法检测肺组织HO-1蛋白的表达。结果 烟雾暴露组mPAP（29.1±1.0mmHg）、RVHI（0.29±0.004）较对照组（16.1±1.0mmHg、0.21±0.005）升高（P＜0.01），HO-1mRNA是对照组的（2.82±1.77）倍；与烟雾暴露组相比,辛伐他汀组mPAP（21.3±0.7mmHg）、RVHI（0.25±0.004）明显降低（P＜0.01），HO-1mRNA明显升高（P〈0.05），是对照组的（7.56±2.91）倍；Western blot及免疫组化结果显示烟雾暴露组大鼠HO-1表达增强，辛伐他汀治疗后表达进一步增强。结论 辛伐他汀降低慢性阻塞性肺疾病所致肺动脉高压，其机制和诱导HO-1表达增加有关。Objective To investigate the roles of HO-1 in the pathogenesis of smoking-induced pulmonary hypertension （HP） and the impact of lipid-lowering therapy on it. Methods An animal model of pulmonary hypertension was prepared by exposing rats to cigarette smoke. The 24 SD rats were randomly divided into three groups： control group, the smoke exposure group and the simvastatin group. The smoke exposure and simvastatin groups were exposed to cigarette smoke in smoking boxes. The simvastatin group was given simvastatin, once a day, since the date of smoke exposure. Four months later, the body weight, the pulmonary artery pressure and the right ventricular hypertrophy ratio of rats were measured, and pathological morphology of lung tissue was observed. The expression of HO-1 protein in rat lung tissue was measured by immunohistochemistry, western blot and real-time RT-PCR. In addition, the effect of simvastatin on its expression was examined. Results PH was pathologically confirmed in rats of the smoke exposure and simvastatin groups. Compared with control group, the pulmonary artery pressure（29.1±1.0 mmHg） and the right ventricular hypertrophy ratios （0.29±0.004） of rats was significantly increased （P〈0.01） in smoke exposure group. Compared with smoke-exposed group, the pulmonary artery pressure（21.3±0.7mmHg） and the right ventricular hypertrophy ratios（0.25±0.004）increased significantly （P 〈 0.01） in the simvastatin group. Real-time RT-PCR results indicated mRNA expression of HO-1 in the smoke exposure group is in the control group （2.82 ＋ 1.77） times （P 〈 0.01）. HO-1mRNA in the simvastatin treatment is in the control group （7.56±2.91） times （P 〈 0.01） . Immunohistochemical and western blot results revealed that the expression of HO-1 proteins in lung tissue was higher in the smoke exposure group than in the control group; deeply increased expression of HO-1 proteins were observed in the simvastatin group compared with the smoke exposure group. Conclusion： H

关 键 词：慢性阻塞性肺疾病 肺动脉高压 吸烟 血红素氧合酶1 辛伐他汀 

分 类 号：R563.9[医药卫生—呼吸系统] R544.1[医药卫生—内科学]