Experimental Study For Bilirubin In Protection Against LPS-induced Acute Lung Injury In Rats

Objectiver;To investigate the relationship between the expression of nuclear factor kappa B(NF-кB) and intercelluar adhesion molecule-1(ICAM-1) as well as the mechanisms of bilirubin ,an effective antioxidant,in the prevention in acute lung injury (ALI). Methods: (1)Lipopolysaccharide (LPS) (5mg/kg body weight) was intravenously injected into the sublingual vein of male Wistar rats(200-250g).Execute respectively at lh,2h,6h and 24h after LPS injection.Then histopathological examination and biological markers were measured for the lung specimens to determine the best time of ALI animal model.(2)ALI animal model was performed using male Wistar rats(200-250g) by LPS 2h.The rats were randomly divided into five groups: control group,LPS 2h group,high dose of pre-treatment bilirubin +LPS 2h group,low dose of pre-treatment bilirubin +LPS 2h group,solvent control group.Histopathologicalexamination and biological markers were measured for the lung specimens.The expression of protein in lung tissues about ICAM-1, NF-кB and I-кBa (the inhibitory protein of NF-KB) as well as oxidative/antioxidative parameters in the homogenate of the rat lungs were determined.Results: In LPS 2h group ,the biological markers of ALI including lung index (LI),the contents of total protein,cell counts and neutrophil percent in bronchoalveolar lavage fluid(BALF),lung permeability index(LPI) significantly increased compared with control group (P<0.001).Moreover,pathologic changes decreased.Further ,it was found that either the ICAM-1 and NF-кB expression in the lung tissues of LPS group or the contents of MDA in the homogenate of the lung tissues were significantly high (P<0.001 vs control group).But I-KBa was decreased (P<0.01).The contents of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) was decreased too(P<0.01,P<0.05).A pretreatment with bilirubin inhibited the LPS-induced changes in lung injury parameters and the induction of NF-кB express.Furthermore,these inhibitory effects of bilirubin correlatedwith a degradation of LPS-induced I-кBa in lung tissues.Bilirubin also substantially reduced the ICAM-1 and suppressed neutrophil recruitment.Conclusions:1.ALI animal model was performed by LPS and detected including histopathological and biological examination.It was confirmed that the model was success and LPS 2h was the best time.It could be used in investigation.2.The important mechanism in ALI,might involve LPS-triggered the degradation of I-KBa and the activation of NF-кB ,in turn the expression of ICAM-1.3.Bilirubin has an obvious protective effect on ALI,which preventive and therapeutic effects of bilirubin on ALI might be related to:(1)the scavenging of oxygen free radical and the increasing of the functioning in antioxidative system.(2)bilirubin pretreatment blocked oxygen free radical-amediated I-кBa degradation and inhibit NF-KB translocation.(3)bilirubin pretreatment inhibited the express of ICAM-1 through the inhibition of NF-кB activation.