Effects Of Dobutamine On Acute Lung Injury In Rabbits Of Septic Shock

ObjectiveThe purpose of this experiment was to study the method of constructing the model of acute lung injury(ALI)in rabbits of septic shock by cecal ligation and puncture combined with intravenous injection of endotoxin,investigate the alteration of aquaporin 5 in ALI induced by septic shock and explore the effect of different doses of dobutamine on ALI in rabbits with septic shock and to clarify the possible mechanism,thus providing a new clinical method in the treatment of ALI.MethodsThe rabbits model of septic shock was made by cecal ligation and puncture combined with intravenous injection of endotoxin,70 male New Zealand white rabbits were randomly divided into five groups(14 rabbits in each group): sham operation group(Group A),ALI group(Group B),low-dose dobutamine group(Group C),medium-dose dobutamine group(Group D)and high-dose dobutamine group(Group E),7 rabbits from each group were sacrificed at 3 h and 6 h after septic shock.The level of cyclic adenosine monophosphate(c AMP)in lung tissue was detected by ELISA.The expression of aquaporin 5(AQP5)protein was determined by western blotting and immunohistochemical analysis.The wet to dry weight(W/D)ratio was measured.The pathological and ultrastructural changes of lung tissue were evaluated by optical microscopy and electron microscope,and lung injury score was assessed.The differences among the different groups were analyzed by one-way ANOVA(LSD test).ResultsThe level of c AMP and expression of AQP5 protein in lung tissue at 3 h and 6 h was dramatically lower in group B than those in group A(P<0.001),while the W/D ratio was obviously higher in group B than those in group A(P<0.05).Compared with group B,the level of c AMP and AQP5 protein expression in lung tissue was significantly increased at 6 h in group C(P<0.001),while the W/D ratio in group E was decreased obviously(P<0.05).Compared with group C and D,the level of c AMP and the expression of AQP5 protein at 3 h and 6 h in group E increased significantly(P<0.01).The pathological and ultrastructural injury of lung tissue was more serious in group B than those in group A and the lung injury scores were obviously higher(P<0.01).The degree of lung pathological and ultrastructural lesion was ameliorated after administration of dobutanmine.Additionally,histological scores decreased significantly(P<0.01).ConclusionsDobutamine could improve ALI induced by endotoxin shock and high-dose dobutamine had better effects,the mechanism of protective effect may involve in increasing the level of c AMP and up-regulating the AQP5 protein expression.