Relationship of p38MAPK,NF-κB and HO-1 in LPS-induced acute lung injury in rats

AIM: To investigate the relationship of p38 mitogen-activated protein kinases ( p38MAPK) ,nuclear factor-kappa B ( NF-κB) and heme oxygenase-1 ( HO-1) in acute lung injury ( ALI) in rats. METHODS: Forty male Wistar rats were divided into 5 groups ( n = 8) at random: control group or normal saline group ( NS group) ,lipopolysaccharide group ( LPS group) ,Hemin ( inducer of HO-1) + LPS group,ZnPPIX ( inhibitor of HO-1) + LPS group and SB203580 ( inhibitor of p38MAPK) + LPS group ( SB + LPS group) . Six hours after endotracheal instillation of LPS or NS, the ratio of neutrophils and the protein contents in bronchoalveolar lavage fluid ( BALF) of right lung,the ratio of wet/dry weight ( W/D) of the superior lobe of right lung,and arterial blood gas analysis ( ABG) were examined. The protein levels of p38MAPK and NF-κB in the lower lobe of right lung were detected by Western blotting. The protein expression of HO1 in the middle lobe of right lung was measured by the method of immunohistochemisty. The structure of the lung was evaluated under light microscope. RESULTS: Compared with NS group,the ratio of neutrophils and protein contents in BALF,the ratio of W/D,the protein levels of HO-1,p38MAPK and NF-κB were obviously higher,and arterial oxygen pressure ( PaO2) ,partial pressure of carbon dioxide in artery ( PaCO2) and bicarbonate content ( HCO3-) were significantly lower in LPS group,Hemin + LPS group,ZnPPIX + LPS group and SB + LPS group ( P 0. 05 or P 0. 01) . The ratio of neutrophils and proteins in BALF,the ratio of W/D,the protein levels of p38MAPK and NF-κB were significantly lower,the protein level of HO-1 was obviously higher in Hemin + LPS group and SB + LPS group than those in LPS group ( P 0. 05) ,while the changes of the parameters in ZnPPIX + LPS group were in a contrary manner ( P 0. 05) . No significant difference of the parameters between Hemin + LPS group and SB + LPS group ( P 0. 05) was found. The structures of the lung tissues in LPS group were severely damaged and even severer damages were observed in ZnPPIX + LPS group. The structural changes of the lung tissues in Hemin + LPS group and SB + LPS group were slighter. CONCLUSION: p38MAPK/NF-κB and HO-1 are inhibited by each other and the effects of them are independent on the acute lung injury.