Protective effects of p38MAPK inhibitor on acute necrotizing pancreatitis associated lung injuries in

Objective To investigate the protective effects of p38MAPK inhibitor SB203580 on acute necrotizing pancreatitis associated lung injuries in rats.Methods Fifty-four SD male rates were randomly divided into 3 groups,including control group,ANP group,SB203580 group with 18 rats in each group.ANP was induced by intraperitoneal injection of L-arginine solution. Rats in control group were intraperitoneally injected with same amount of saline.Before ANP induction,the rats in SB203580 group received 10 μmol/L SB203580 dissolved by dimethyl sulfoxide at a dose of 5mg/kg weight via intraperitoneal injection.The rats were sacrificed at 3,6,and 12 h after operation,the serum levels of amylase,TNF-α,IL-6 was determined.Pathological changes of pancreas and lung were observed.The wet/dry (W/D) weight ratio of lung and MPO were measured.CINC mRNA of lungs was determined by RT PCR. Expression of phosphated-p38MAPK (p-p38MAPK) protein was evaluated by Western blotting.Results The serum levels of amylase,TNF-α,IL-6and wet/dry (W/D) weight ratio of lung,MPO activity,CINC mRNA and p-p38MAPK protein expression of lungs were (1035 ±73)U/L,(0.94 ±0.16)μg/L,(4.77 ±0.86) μg/L,3.92 ±0.29,(0.39 ±0.02)U/g,0.28 ±0.04,0.09 ±0.04 in control group at 6 h after operation,and the corresponding values were (5848 ±656) U/L,(3.84 ±0.32)μg/L,(103.54 ± 15.32)μg/L,4.97 ±0.47,(1.03 ±0.08) U/g,0.62 ±0.06,0.52 ±0.14 in ANP group,while they were (4259 ±286) U/L,( 1.64 ±0.21 ) μg/L,(76.56 ± 11.46) μg/L,4.32 ±0.34,(0.78 ±0.05)U/g,0.37 ±0.04,0.27 ±0.08 in SB203580 group.The values in ANP group were significantly higher than those in control group,and the values in SB203580 group were significantly lower than those in ANP group,but they were still significantly higher than those in control group ( P ＜ 0.01 ).Conclusions SB203580 may attenuate injury of lung and pancreas in ANP by blocking p38MAPK signal transduction pathway,and decreasing the production of inflammatory cytokines. Key words: Pancreatitis, acute necrotizing;  p38 mitogen-activatal protein kinase; SB203580; Acute lung injury