The Effect Of Methylprednisolone On High Mobility Protein1Expression In LPS-induced Acute Lung Injury

Objective:to explore the function of high mobility group boxl (HMGB1) in rats’lung tissue with acute lung injury induced by lipopolysaccharide and the intervention effect of methylyprednisolone injection by detecting the HMGB1mRNA and its protein expression in different periods.Methods:fifty-four male SD rats were randomly divided into three groups.each group hALIghteen rats:control group(n=18injected1ml/kg saline through tail vein after the2ml/kg saline was injected), ALI group(n=18, injected1ml/kg saline through tail vein after the6mg/kg lipopolysaccharide was injected), MPN group(n=18, injected20mg/kg methylprednisolone through tail vein after the6mg/kg lipopolsaccharide was injected). The rats’changes of ethology were observed. Six rats of each group were killed at the twelve hour, twenty-four hour and thirty-six hour after the lipopolsaccharide was injected. Rats’blood from carotid artery was collected for vigor analysis. One part of the rats’lung was obtained and used for histopathology, immunohistochemistry and reverse transcription-polymerase chain reaction(RT-PCR). The HMGB1mRNA and its protein expression was measured by immunohistochemistry and RT-PCR. The another part of the rats’lung was used for the determination of the proportion of wet and dry(W/D).Results:1Changes of general conditions in each group:the rats in the ALI group curled up and showed a vertical hair, Shortness of breath, unresponsive, anorexy,less activity, changes of excrement. These symptoms obviously in24h,better in36h. These symptoms in MPN group were relieved at the same time after the protection of the methylprednisolone.2> Changes of the proportion of wet and dry(W/D) in each group:in ALI group increased significantly,much higher than that in control group (P<0.01). But it had no statistical difference in each time point (P>0.05).The proportion of wet and dry(W/D) in MPN group also increased, higher than that in control group (P<0.01),but lower than that in ALI group.3、Changes of blood gas analysis in each group:in control group,the blood gas analysis was normal,compared with the significant decrease of the oxygen pressure in ALI group (P<0.05). In MPN group the oxygen pressure decreased,but litter higher than that in ALI group.4、Changes of histopathology of rats’lung tissue in each group:in control group, the histopathology of rats’lung tissue showed no inflammatory cell in the alveolar interstitial and alveolar space,the lobular structure was clear. In ALI group, it showed different degrees of swelling of the lung surface scattered congestion spots, alveolar wall widened,alveolar and pulmonary vascular showed obvious congestion and edema, you kan see the leakage of red blood cell in the alveolar space, the infiltration of inflammatory cell in the alveolar interstitial and alveolar space. These symptoms were worse and worse, obviously in24h,and got better in36h. These symptoms in MPN group relieved after the protection of methylprednisolone.5、Changes of the expression of HMGB1mRNA and its protein in each group:lung tissue of control group expressed little HMGB1mRNA and its protein,and it increased quickly in ALI group and MPN group with peak levels being present at24h,which significantly higher than that in control group (P<0.05). The expression of HMGB1mRNA and its protein in MPN group was less than that in ALI group (P<0.05)Conclusion:1、the expression of HMGB1mRNA and its protein increased quickly after acute lung injury with peak levels being present at24h,which significantly higher than that in control group.lt showed HMGB1mRNA and its protein had a persistent high levels of expression on the stage of inflammation.This uncontrolled inflammation reaction will contribute to the development of acute lung injury.2、The expression of HMGB1mRNA and its protein was less than that in ALI group after the methylprednisolone was injected, the methylprednisolone reduced inflammatory response in acute lung injury, which conjected that methylprednisolone had a protective effect to acute lung injury induced by lipopolysaccharide.