Effects of dobutamine on acute lung injury in rabbits of septic shock

Objective To explore the effect of different doses of dobutamine on acute lung injury (ALI) in rabbits with septic shock and to clarify the possible mechanism.Methods The 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 groups):shamc operation group (group A),ALI group (group B),dobutamine low-dose group (group C),dobutamine medium-dose group (group D) and dobutamine high-dose group (group E),7 rabbits from each group were sacrificed 3 h and 6 h after septic shock.The level of cyclic adenosine monophosphate (cAMP) in lung tissue was detected by ELISA.The expression of aquaporin 5 (AQP5) protein was determined by western blotting.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).Results The level of cAMP and expression of AQP5 protein in lung tissue at 3 h and 6 h were dramatically lower in group B than those in group A (3.53 ±0.43) pmol/mLvs.(21.18 ±0.62) pmol/mL; (0.44 ± 0.04) pmol/mLvs.(0.99±0.06)pmol/mL; (2.71±0.56)pmol/mLvs.(21.78±0.62)pmol/mL; (0.29 ±0.05) pmol/mLvs.(0.91 ±0.06) pmol/mL; all P ＜0.001,while the W/D ratio was obviously higher in group B than those in group A (all P ＜0.001).Compared with group B,the level of cAMP and AQP5 protein expression in lung tissue were significantly increased at 6 h in group C (8.48 ±0.61) pmol./ mLvs.(2.71±0.56) pmol/mL,P＜0.01; (0.49 ±0.04) pmol/mLvs.(0.29 ±0.05) pmol/mL,P=0.001 and at3 hand6 hin groupDandE (10.86±0.66) pmol/mLvs.(3.53±0.43) pmol/mL; (0.60±0.05) pmol/mLvs.(0.44±0.04) pmol/mL; (13.80±0.49) pmol/mLvs.(2.71±0.56) pmol/mL; (0.64 ± 0.03) pmol/mLvs.(0.29 ± 0.05) pmol/mL; (15.57 ± 0.60) pmol/mL vs.(3.53±0.43) pmol/mL; (0.91 ±0.05) pmol/mLvs.(0.44 ±0.04) pmol/mL; (19.30±0.42) pmol/mL vs.(2.71 ±0.56) pmol/mL; (0.89 ±0.08) pmol/mL vs.(0.29 ±0.05) pmol/mL; all P ＜ 0.01,while the W/D ratio in group E was decreased obviously (P =0.002; P =0.001).Compared with group C and D,the level of cAMP and the expression of AQP5 protein at 3 h and 6 h in group E increased significantly (all P ＜0.01.The pathological and ultrastructural changes of lung tissue were more intensive 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).Conclusions Our study demonstrated that dobutamine could improve ALI induced by endotoxin,the mechanism of protective effect may involve in increasing the level of cAMP and up-regulating the AQP5 protein expression,and high-dose dobutamine had better effects. Key words: Acute lung injury;  Septic shock;  Dobutamine;  Aquaporin 5;  Cyclic adenosine monophosphate