Experimental Study Of Protective Effects Of Endothelin-1 Receptor Antagonist (BQ-123) In Rats Lung Ischemia-reperfusion Injury

Objective:Lung ischemia-reperfusion injury widely exists after pulmonary artery angioplasty and bronchoplasty.So,try to shorten ischemia time,in the tolerance time of the organization to restore blood perfusion,is the key to surgical operation success.This study through establishment of rat lung ischemia-reperfusion injury animal model,discusses the lung function and structure changes in different periods of occluding pulmonary artery and hilum of lung,and the lung protection of endothelin-1 receptor antagonist.Materials and methods:42 Wistar rats were randomly divided into 7 groups,6 rats in each group:groupâ… ,sham operated,blood flow of left lung was not blocked after entry into the thorax;groupâ…¡:occluding left pulmonary artery for 45min followed by 2 hours reperfusion;groupâ…¢:occluding left pulmonary artery for 60min followed by 2 hours reperfusion;groupâ…£:occluding left hilum of lung for 30min followed by 2 hours reperfusion;groupâ…¤:occluding left hilum of lung for 45min;groupâ…¥:BQ-123(1mg/kg)was given by intravenous dropping before occluding left pulmonary artery for 60min followed by 2 hours reperfusion;groupâ…¦:BQ-123 (1mg/kg) was given by intravenous dropping before occluding left hilum of lung for 45min followed by 2 hours reperfusion.Rats were anesthetized by chloral hydrate (0.3ml/100g),they were connected to little animal ventilator after tracheotomy. Respiratory rate:55bpm,tidal volume:Sml/kg,I:E=1:2,oxygen concentration:35%. Experimental rat model of lung ischemia-reperfusion was established by occluding left pulmonary artery and occluding left hilum of lung,and then restored blood perfusion for 2 hours.The wet to dry weight ratio of lung tissue(W/D),the mean pulmonary artery pressure(mPAP),arterial oxygen tension(PaO₂) and plasma endothelin-1(ET-1)were measured respectively in differently groups,the expressions of Fas and Fas-L protein in the lung tissues of ischemia-reperfusion injury area were measured by SABC immunohistochemical technique,the pathological and ultrastructured changes after lung tissue ischemia-reperfusion injury were also observed.All datas were expressed as mean±SD,and comparisons between groups wre analyzed with one-way ANOVA test.P value less than 0.05 were statistically considered significant.Results:Between groupâ… and groupâ…¡,â…£,W/D,mPAP,ET-1 and the PaO₂ were no difference(p＞0.05).The marked increase of W/D,mPAP,ET-1 and the decrease of PaO₂,together with the higher expression of Fas and Fas-L protein were observed in groupâ…¢,â…¤(P＜0.05).The hyperemia and edema of alveolar and bronchus epithelial became more and more obviously,the infiltration of erythrocyte and alveolus interval widen under lightmicroscope.The ultrastructure of the typeâ…¡alveolar cells showed that lamellar body sublatioed,the mitochondria and endocytoplasmic reticulum swelled severely,the capillary epithelial cell apoptosised more,the proliferation of collogen became more.Compared with groupâ…¢,W/D,mPAP,ET-1,expression of Fas and Fas-L protein were decreased,while PaO₂ were increased in groupâ…¥(P＜0.05),and W/D,mPAP,ET-1,expression of Fas,Fas-L protein were decreased,while PaO₂ were increased in groupâ…¦than in groupâ…¤(P＜0.05),under lightmicroscope,the hyperemia and edema of alveolar and bronchus epithelial were less than in groupâ…¢,â…¤.The ultrastructure of the typeâ…¡alveolar cells showed obviously difference in groupâ…¢,â…¤,the lamellar body sublatioed little,the mitochondria swelled lightly,the capillary epithelial cell apoptosised less,the proliferation of collogen became rare.Between groupâ…¡andâ…¤,there were a lot of differences,maybe they were caused by bronchial arterial compensate the oxygenation of pulmonary.Conclusion:Occluding hilum of lung 30min is the security time limit,while occluding pulmonary artery 45min is the security time limit.The lung ischemia-reperfusion injury is significantly after 60min of occluding left pulmonary artery and 45min of occluding left hilum of lung,endothelin-1 receptor antagonist can decrease the lung tissue ET-1 level and the percentage of apoptotic and necrotic cells after lung ischemia-reperfusion injury,improve the lung function.These finding indicated that endothelin-1 receptor antagonist can provides protective effects on lung ischemia-reperfusion injury.bronchial arterial compensate the oxygenation of pulmonary.