兔急性肺血栓栓塞及溶栓后TXA_2、PGI_2及ET-1水平的变化与血流动力学相关性研究

The correlation study between levels of TXA_2,PGI_2,ET-1 and hemodynamic changes after thrombolysis in acute pulmonary embolism of rabbit

目的:探讨兔急性肺动脉血栓栓塞时血清炎症因子血栓素A2(TXA2)、前列环素(PGI2)和肺血管内皮、支气管和肺泡上皮等部位内皮素1(ET-1)变化和血流动力学指标变化及尿激酶(UK)溶栓的影响。方法:24只大耳白兔随机分为对照组、急性肺栓塞(acute pulmonary thromboembolism,APTE)模型组、尿激酶(UK)治疗组,每组8只。采用自体血栓回输法建立动物模型。常规于造模前、造模后1、2、4、8h放免法测定血清TXA2、PGI2,漂浮导管监测血流动力学指标,最后免疫组化法检测肺血管内皮、支气管和肺泡上皮各部位ET-1的表达水平。结果:①放免法测定结果:对照组各时间点无显著差异。模型组1h升高,4h达高峰,其后开始降低,1、2、4h点与对照组比较都有统计学意义(P<0.01)。UK组1h升高,2h达高峰,4h后开始下降,UK组高峰值较模型组低,1、2、4h UK组与模型组两者有统计学意义(P<0.01)。各组术前和8h无统计学差异(P>0.05);②血流动力学监测结果:对照组各时间点肺动脉平均压(PAMP)、中心静脉压(CVP)都无明显变化,模型组及UK组PAMP、CVP栓塞后立即升高,2h升至最高,后有所下降,1、2、4、8h模型组和UK组两组与对照组均有统计学差异(P<0.01);UK组与模型组1、2h有统计学差异(P<0.01),4、8h无统计学差异(P>0.05);③免疫组化检测显示:模型组ET-1蛋白表达的相对含量显著高于对照组,UK组与对照组比较无统计学差异。结论:细胞因子TXA2、PGI2、ET-1参与了APTE早期肺血管阻力增加,APTE早期溶栓可明显降低TXA2、PGI2、ET-1以及减轻肺血管阻力的增加。

Objective：To study the expression levels of thromboxane A2（TXA2） and prostacyclin （PGI2） in the plasma,endothelin-1 （ET-1）in vascular endothelium,bronchial and alveolar epithelia of lungs,and hemodynamic changes in acute pulmonary thromboembolism（APTE） of rabbit,and to explore the effects of thrombolytic（urokinase,UK）on their expressions. Methods：Twenty four rabbits were randomly divided into a control group,a APTE model group,a UK therapy group,with 8 rabbits each. The APTE model was established by intravenous injection of autologous blood clots. The plasma’s concentrations of TXA2 and PGI2 were examined by radioimmunoassay before and 1 h,2 h,4 h,8 h after injection. The hemodynamic monitoring were used by float catheter. The expression levels of ET-1 in lung vascular endothelium,bronchial and alveolar epithelia were examined by immunohistochemistry. Results： ①The radioimmunoassay showed that TXA2 and PGI2 had no diference in the control group at each point;TXA2 and PGI2 in the APTE group increased at 1 h,peaked at 2 h,decreased at 4 h,which also were higher than those in the control group at 1 h,2 h, 4 h（P〈0.01）. In the UK group,TXA2 and PGI2 increased at 1 h,peaked 2 h,decreased after 2 h,also decreased faster than those in the APTE group at 1 h,2 h and 4 h,respectively （P〈0.01）. There were no differences in TXA2 and PGI2 before injection and 8 h after injectionin in each group（P〉0.05）. ②Hemodynamic monitoring showed that the PAMP and CVP were no change in the control group;and PAMP and CVP in the APTE group and UK group increased immediately after embolism,peaked at 2 h,then decreased, which also were higher than those in the control group at 1 h,2 h,4 h,8 h （P〈0.01）. In the UK group PAMP and CVP also decreased faster than those in the APTE group at 1 h,2 h respectively （P〈0.01）. There were no differences at 4 h and 8 h between the APTE group and the UK group. ③The immunohistochemistry results showed in the APTE,the expression levels of ET-1 in lung vascular endothelium,bronchial and alveolar epithelia were significantly higher compared with those in the control group. The UK group was significantly lower in ET-1 as compared to the APTE group. Conclusion：After APTE,TXA2,PGI2,ET-1 participated increasing of pulmonary vascular resistance,and early thrombolytic treatment could decrease TXA2,PGI2,ET-1,also relieved pulmonary vascular resistance.