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目的 通过客观评估大鼠模型的右心室压力、肺动脉压力、心输出量、心指数及全肺阻力指数(TPRI)等指标,建立更完善的肺动脉高压模型大鼠血流动力学评价系统,更客观准确地评价肺动脉高压大鼠的疾病严重程度及活动耐量.方法 SPF级雄性SD大鼠10只,采用随机数字表法分为对照组与模型组,每组5只.模型组腹腔注射SU5416(20 mg/kg)放入10％氧浓度的缺氧箱,21 d后置于常氧环境14 d,对照组在常氧环境下饲养35 d.造模结束后将大鼠麻醉,建立机械通气.沿右侧胸骨旁线切开皮肤,剥离右侧胸大肌,分离并结扎肋间动脉,剪开第3、4肋骨,暴露心脏,游离主动脉干.把超声血流仪探头套在剥离好的主动脉干段,实时记录主动脉时间-血流速波形,计算心输出量.然后将连接有压力感受器的针头插入右心室内,系统采集右心室时间-压力波形.待波形稳定约30 s,将插管末端经肺动脉入口送至肺动脉干采集肺动脉时间-压力曲线.结果 对照组与模型组的右心室收缩压(RVSP)分别为(23±5)和(56±13)mmHg(1 mmHg=0.133 kPa),肺动脉收缩压(PASP)分别为(23±4)和(58±15)mmHg,肺动脉舒张压(PADP)分别为(9.7±1.9)和(30.3±7.0)mmHg,肺动脉平均压(mPAP)分别为(14.1±2.7)和(41.9±8.0)mmHg,组间差异均有统计学意义(均P<0.05).模型组与对照组的心指数分别为(0.54±0.08)和(0.40±0.09)ml·min-1·g-1,组间比较差异有统计学意义(P=0.02).计算模型组和对照组的衍生指标TPRI,分别为(0.27±0.03)和(0.06±0.01)mmHg·ml-1·min-1·kg-1,组间比较差异有统计学意义(P<0.001).病理结果显示模型组肺动脉中膜增厚,肺动脉重塑.结论 本研究建立了一种同时测定大鼠心输出量、右心室和肺动脉压力的实验方法,更全面评价肺动脉高压大鼠模型的血流动力学改变.

Objective By evaluating the hemodynamic parameters such as cardiac output (CO), right ventricular pressure (RVP), pulmonary artery pressure (PAP) and total pulmonary resistance index (TPRI) in pulmonary hypertension rat model , we established a more comprehensive hemodynamic evaluation system, which objectively evaluated the severity of disease and exercise tolerance in rats with pulmonary hypertension.Methods SD rats were randomly divided into a control group and a model group with 5 rats in each group.The model group was intraperitoneally injected with SU 5416 (20 mg/kg) and placed in an oxygen chamber at a 10％ oxygen concentration for 21 days and then placed in a normoxic environment for 14 days.After modeling, rats were anesthetized and mechanically ventilated .The operator cut the skin along the right paraxial line, detached and ligated the intercostal artery , and then cut off the 3 and 4 ribs, exposing the heart and freeing aortic root about 0.2 cm.The flowmeter probe was set in the dissected aortic segment, and real-time recording time, blood flow waveforms, cardiac output were calculated accordingly. Then the needle attached to the baroreceptor was inserted into the right ventricle and the system acquired the right ventricular time-pressure waveform.After the waveform stabilized for about 30 seconds, the end of the cannula was sent to the pulmonary artery trunk through the entrance of the pulmonary artery to record the time-pressure curve of the pulmonary artery.Results RVSP, PASP, PADP and mPAP in the model group were significantly higher than those of the control group [ RVSP(23.4 ±5.4) mmHg, 1 mmHg =0.133 kPa vs (56.4 ±13.0) mmHg, PASP (22.8 ±4.4) mmHg vs (58.5 ±14.9) mmHg, PADP (9.7 ±1.9) mmHg vs (30.3 ±7.0) mmHg, mPAP (14.1 ±2.7) mmHg vs (41.9 ±8.0) mmHg, all P <0.05 ]. Compared with the control group , the cardiac index in the model group was significantly lower [ CI (0.54 ± 0.08) ml· min-1 · g-1 vs (0.40 ±0.09) ml· min-1 · g-1 , P =0.02 ].Furthermore, compared with the control group,pulmonary vascular resistance index was significantly increased in the model group [ PVRI (0.27 ±0.03) mmHg· ml-1 · min-1 · kg-1 vs (0.06 ±0.01) mmHg· ml-1 · min-1 · kg-1 , P <0.05] .The pathological results also showed that the middle part of pulmonary arterioles in the model group had muscular hypertrophy and muscular pulmonary arterioles , and even plexiform lesions.Conclusion In this study, we established a new method that simultaneously determined several hemodynamic parameters such as RVSP, PASP, PADP, CO, CI and PVRI, which provided a more comprehensive assessment of hemodynamic changes in pulmonary hypertension rat models .