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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 investigate the changes of endothelin-1 (ET-1) and hemodynamics of serum inflammatory factors such as thromboxane A2 (TXA2), prostacyclin (PGI2) and pulmonary vascular endothelium, bronchus and alveolar epithelium in rabbits with acute pulmonary thromboembolism Index changes and urokinase (UK) thrombolysis. Methods: Twenty - four large white rabbits were randomly divided into control group, acute pulmonary embolism (APTE) model group and urokinase group (n = 8). Animal models were established by autologous thrombosis. Routinely before modeling, 1, 2, 4, 8 h after model establishment, serum TXA2 and PGI2 were measured by radioimmunoassay and the floating catheter was used to monitor hemodynamic parameters. Finally, immunohistochemistry was used to detect the expression of ET, -1 expression level. Results: ① radioimmunoassay results: no significant difference between the control group at each time point. The model group was elevated at 1 hour and peaked at 4 hours, then began to decrease. There was statistical significance at 1, 2 and 4 hours (P <0.01). UK peaked at 1 hour, peaked at 2 hours, and then decreased at 4 hours. The peak value of UK group was lower than that of model group. There was significant difference between UK group and model group at 1, 2 and 4 hours (P <0.01). There was no significant difference between before and 8h in each group (P> 0.05) .②The results of hemodynamic monitoring showed that there were no significant changes in PAMP and CVP at all time points in the control group, PAMP and CVP increased immediately after embolization in UK group, and reached the peak at 2 hours after embolization. The levels of PAMP and CVP in 1, 2, 4 and 8 h groups were significantly different from those in control group (P <0.01) The expression of ET-1 protein in the model group was significantly higher than that in the model group at 1 and 2 hours (P <0.01), but no significant difference at 4 and 8 hours (P> 0.05) There was no significant difference between the control group, the UK group and the control group. CONCLUSION: The cytokines TXA2, PGI2 and ET-1 are involved in the early pulmonary vascular resistance increase in APTE. Early thrombolytic therapy of APTE can significantly decrease TXA2, PGI2, ET-1 and decrease the pulmonary vascular resistance.