上腔静脉频谱对大鼠肺动脉高压的评价作用

Application of superior vena cava spectrum in evaluation of therapeutic effects of monocrotaline-induced pulmonary arterial hypertension in rats

目的探讨上腔静脉频谱对野百合碱诱导的大鼠肺动脉高压的评价作用。方法健康成年雄性SD大鼠168只,体重180-220 g,随机选取10只为正常对照组。大鼠腹腔注射2%野百合碱50 mg/kg造模,以肺动脉收缩压大于30 mmHg（1 mmHg=0.133 kPa）为模型成功的标准。第28天造模成功103只,随机选取8只进行模型检测,其余存活大鼠随机分为贝前列素组、西地那非组、波生坦组,每组24只,余23只为安慰剂组。灌胃治疗2周后进行上腔静脉超声检测及右心导管测量右心室压及肺动脉收缩压。结果造模成功并测得肺动脉压力、进行上腔静脉超声检测的大鼠55只。大鼠模型体重减轻,肺动脉压增高,其中波生坦组肺动脉压力最高,与上腔静脉AR/S比值、上腔静脉S波相关性好。超声心动图检测上腔静脉血流频谱提示肺动脉高压大鼠AR/S增高,S波减低,与对照组比较差异有统计学意义（P〈0.01）。Pearson相关示肺动脉收缩压与上腔静脉血流频谱参数AR/S明显相关（右侧AR/S：Y=50.07X＋24.62,R2=0.302,P〈0.01;左侧AR/S：r=0.491,P〈0.01）。从用药后的自然死亡率分析,每组死亡的大鼠出现不同程度胸腹腔积液和心包积液,以安慰剂和波生坦组较重,波生坦组在3种治疗药物中死亡率最高,但差异无统计学意义。肺组织光镜下显示：模型组、安慰剂组及各治疗组大鼠肺小动脉均出现不同程度中膜增厚,管腔变小,平滑肌增生。正常组肺小动脉未见明确异常。结论右上腔静脉频谱AR/S与肺动脉收缩压相关性良好,可作为多普勒超声评价肺动脉高压的参数之一。

Objective To investigate the value of spectrum of superior vena cava（SVC） in estimation of curative effect of monocrotaline induced pulmonary hypertension in rats. MethodsOne hundred and sixty-eight（weight 180-220 g） healthy adult male SD rats were included, with 10 rats as normal controls. Pulmonary hypertension rat models（pulmonary artery systolic pressure greater than 30 mmHg, 1 mmHg = 0.133 kPa） were established by intraperitoneal injection of 2% monocrotaline 50 mg/kg. In twenty-eighth days, 8/103 rats were randomly selected to assess the efficacy of the model. The rest rats were randomly treated with beraprost, sildenafil, bosentan（24 rats/group） and placebo（23 rats）, accordingly divided into four groups. After 2 weeks of treatment, SVC Doppler ultrasound and right ventricular pressure, pulmonary arterial systolic pressure measured with right heart catheter were compared. Results Pulmonary arterial hypertension model was successfully established in 55 rats and they all underwent SVC ultrasound examination. AR/S ratio of the right SVC and S velocity of both the left and right SVCs had a good correlation with the pulmonary arterial pressures. SVC Doppler flow showed significantly increased AR/S and decreased S wave compared with the control group（P〈0.01）. Pulmonary artery systolic pressure was significantly correlated the right SVC AR/S ratio（AR/S of right SVC： Y=50.07X＋24.62, R2=0.302, P〈0.01; AR/S of left SVC： r=0.491, P〈0.01）. Drug efficacy analysis： on analysis of natural mortality after administration, dead rats in each group appeared hydrothorax, ascites and pericardial effusion, which was more severe in placebo and bosentan groups. Bosentan group had the highest mortality. But there was no significant difference among groups（P〉 0.05）. The lung tissue pathology examination showed varied degrees of membrane thickening, lumen narrowing and smooth muscle hyperplasia in all groups. Conclusion The pulmonary arterial hypertension model could be successfully established by intraperitoneal injection of 2% MCT. There was no statistically significant difference in the short-term efficacy of beraprost, sildenafil and bosentan. AR/S of right SVC correlated well with the pulmonary artery systolic pressure and it may be used as one of Doppler ultrasound parameters for evaluation of pulmonary hypertension and its therapeutic effects.