| Objective: The pulmonary embolism is a clinic syndrome caused by endogenous or exogenous embolus obstructs pulmonary artery. Increasing of pulmonary vascular resistance and pulmonary artery pressure is pathophysiological foundation of APE.Embolic effection of"mechanical obstruction"is immediate cause of increasing of pulmonary vascular resistance. In addition, Neurohumor has also possessed important effection on change of pulmonary circulation in embolism earlier period. Lung vascular endothelium damaging after lung embolism releases of lots of vasoactive substances, such as endothelin , AngⅡand UrotensinⅡ.Apelin was found in 1998 to be congaed endogenous ligand for the APJ receptor (a putative receptor protein related to the angiotensin-type 1 receptor), which had been previously designated an"orphan"G-protein-coupled coupled receptor (GPCRs) and firstly identified by the Human Genome Project. The structure of Apelin and APJ is highly conserved among species, suggesting its importantly physiological roles. It is well known that GPCRs represents the greatest proportion of known therapeutic targets.Study shows Apelin might play a role in regulating fluid homeostasis and immune fuction,inhibiting that human immunodeficiency circus infection by blocking the virus co receptor.So far, however, there is little information of the functional roles of Apelin and APJ in pulmonary circulation, but there is sufficient evidence to show that it plays an important role of multi-targets, a wide range of new endogenous protective factor. Apelin-APJ system may have a special role of the maintenance of steady-state of pulmonary circulation and related to the development of lung diseases. Purpose of the experiment is to investigate their effects and the possible mechanisms of pulmonary artery hypertension following APE. Method:sixty-four New Zealand rabbits, weighing 2.5～3.5kg,the male and female were given consideration to, were obstructed the left lower lung artery by inflating gas of 5F Berman sacculus catheter to set up rabbit APE model.The animals were randomly divided into eight groups:(1) control group(n=8), (2)sham operation group(n=8), (3)embolism 1h group(n=8), (4)embolism 2h group(n=8), (5)embolism 4h group(n=8), (6)embolism 8h group(n=8) (7)embolism 12h group(n=8) (8)embolism 24h group(n=8). We monitored the pulmonary arterial mean pressure (PAMP) at pre-embolization, embolization instantly, embolization1h, 2h, 4h, 8h, 12h and 24h. We detected the content of Apelin and APJ in plasma by ELISA method, and the content of AngⅡby Radioimmunoassay method at embolization1h, 2h, 4h, 8h, 12h and 24h. We monitored the relationship between the three and pulmonary artey hypertension.Results:1.The changes of lung hemodynamics before and after embolism:PAMP was rapidly increased after embolis, and was obvously higher than pre-embolization and sham group lever (P<0.05, respectively). PAMP was decreased gradually at embolization 0.5h,1h,but still higher significantly than pre-embolization(P<0.05,respectively). PAMP was decreased to the pre-emblization and sham group level at embolism 2h 4h and 8h. PAMP was increased again at embolism 12h and 24h, and was higher than pre-embolization and sham group lever (P<0.05, respectively)2.The change of Apelin in plasma and lung homogenate: Between the groups in plasma and lung homogenate in Apelin trends in basically the same; The content of plasma Apelin were higher significantly at embolization 1h, 2h, 4h, 8h than control group and the sham operation group(P<0.05 ,respectively).At the embolization 2h group, the content of plasma Apelin achieved peak. The content of plasma Apelin gradually decreased at embolismation 8h, 12h and 24h. The content of plasma Apelin at the embolization 12h and 24h group are significant lower than the control group. (P﹤0.05, respectively).3.The change of APJ in plasma and lung homogenate: Between the groups in plasma and lung homogenate in APJ trends in basically the same ;The content of plasma APJ were higher significantly at embolization 1h, 2h, 4h, 8h than control group and the sham operation group(P<0.05,respectively).At the embolization 2h group, the content of plasma APJ achieved peak. The content of plasma APJ gradually decreased at embolismation 8h, 12h and 24h. The content of plasma APJ at the embolization 12h and 24h group are significant lower than the control group. (P﹤0.05, respectively).4.The changes of AngⅡin plasma and lung homogenate: Between the groups in plasma and lung homogenate in AngⅡtrends in basically the same;the content of plasma AngⅡwere higher significantly at embolization lh, 2h, 4h, 8h, 12h and 24h than the control group.(P<0.05,respectively), the content of plasma AngⅡwere higher at embolization 12h and 24h than embolization 1h, 2h, 4h and 8h. (P<0.05,respectively)and gradually increased accompanied the prolongation of embolization.However, the plasma concentration of AngⅡmultiples higher than the control group was significantly higher than in lung homogenate concentration of AngⅡmultiples higher than the control group.5.The relation between AngⅡ/Apelin ratio and pulmonary artery hypertension: the ratio were not significant difference at control group, sham group and embolization 1h,2h, 4h, 8h (P>0.05, respectively). The ratio at embolization 12h and 24h were higher than the control group and sham group lever (P<0.05, respectively).6.The coefficient correlation was analyzed: Statistic analysis showed that the content of plasma AngⅡand Apelin were negative correlation(r=﹣0.81 P <0.05); the content of plasma AngⅡ/Apelin ratio and PAMP were correlated significantly positively (r=0.703 P<0.05). Conclusion:1.Elevated pulmonary vascular resistance, acute pulmonary hypertension and other hemodynamic changes together form the foundation of APE injury.2.Increased pulmonary vascular resistance, acute pulmonary hypertension and so on, form the base of hemodynamic derangements, which may lead to pulmonary injury in APE.3.The mechanism of Apelin to participate pulmonary vascular response may be related to the antagonist of AngⅡ.4.Apelin as a original factor can reflect the pulmonary artery pressureof APE.
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