野百合碱诱导运动诱发肺动脉高压大鼠模型的建立及他达那非早期干预效果

Establishment of exercise induced pulmonary hypertension rat model induced by monocrotaline and early intervention effect of tadalafil

目的:建立运动诱发肺动脉高压(exercise induced PH,EiPH)大鼠模型,早期明确诊断,及时给予治疗,评估大鼠PH进展、肺血管重塑情况及生存率。方法:雄性Sprague Dawely(SD)大鼠60只,体质量200~220 g,大鼠注射野百合碱(monocrotaline,MCT)(60 mg/kg)后,分别在第1、3、5、7、9天检测大鼠静息状态下平均肺动脉压力(mean pulmonary artery pressure,mPAP)及运动状态下峰值mPAP(maximum mPAP,mPAPmax)。选取大鼠静息mPAP<25 mmHg且运动状态下mPAPmax>30 mmHg定义为EiPH组;将大鼠静息mPAP≥25 mmHg随机分为静息PH(rest PH,rPH)组和PH组;注射生理盐水的大鼠为对照组。EiPH组与rPH组大鼠分别给予等量他达那非灌胃2周。各组大鼠于实验终点完成超声心动图检查,改良右心导管测压,留取心肺组织。结果:MCT注射后第7天,大鼠运动状态下mPAPmax较对照组明显升高[(38.5±2.7)mmHg vs.(27.24±0.46)mmHg,P=0.000]。MCT注射后第35天,rPH+T组大鼠静息mPAP升高[(26.67±0.11)mmHg vs.(35.23±0.47)mmHg,P=0.000]、右室肥厚指数增加(0.34±0.01 vs.0.46±0.02,P=0.004)、肺动脉中膜厚度百分比增加(44.4%vs.55.6%,P=0.008)。结论:本研究成功建立EiPH大鼠模型。他达那非干预实验结果表明,早期阶段给予PH大鼠治疗的降压及抑制肺血管重构效果优于同等剂量药物的晚期用药。

Objective:To establish exercise induced pulmonary hypertension(EiPH)rats model,diagnose in the early phase and treat as soon as possible,so as to assess the pulmonary hypertension(PH)progression,pulmonary artery remodeling and survival rate.Methods:Sixty male Sprague Dawely(SD)rats,with weight 200 to 220 g,were intraperitoneally injected with monocrotaline(MCT,60 mg/kg).After injecting MCT,the mean pulmonary artery pressure(mPAP)under resting and exercising condition and maximum mPAP(mPAPmax)under exercising condition on the 1st,3rd,5th,7th and 9th day were measured.Rats with resting mPAP<25 mmHg and exercising mPAPmax>30 mmHg were classified into EiPH group;rats with resting mPAP≥25 mmHg were randomly divided into resting PH(rPH)group and PH group;rats with injection of saline were classified into control group.Rats in the EiPH and the rPH group were given same dose tadalafil(T)by gavage for two weeks.Echocardiography was performed at the end of experiment,right heart catheter was improved to measure the pulmonary artery pressure and the cardiopulmonary tissue was taken and kept.Results:On the 7th day after MCT injection,the exercising mPAPmax in the MCT group was higher than that in the control group[(38.5±2.7)mmHg vs.(27.24±0.46)mmHg,P=0.000].On the 35th day after MCT injection,resting mPAP in the rPH+T group was increased[(26.67±0.11)mmHg vs.(35.23±0.47)mmHg,P=0.000],right ventricular hypertrophy index was raised(0.34±0.01 vs.0.46±0.02,P=0.004)and the percentage of pulmonary artery wall thickness(44.4%vs.55.6%,P=0.008)was magnified.Conclusion:The EiPH rat model was successfully established.According to tadalafil intervention experiment,effectiveness of lowering blood pressure and inhibiting pulmonary vessel remodeling in the early phase is better than treating with a same dose drugs in the late phase.