| Objective:To observe the expression level of NF-?B?HIF-1??COX-2 on SD rats with LPS-induced acute lung injury,and to investigate the mechanism of 2ME2 intervention on the role of acute lung injury induced by LPS.To find new methods for the treatment of acute lung injury.Methods: 1.The healthy male SD rats were randomly divided into five groups(n=300,normal group=60,acute lung injury model group=60,vehicle group=60,low dose 2ME2 treatment group(8mg/kg)=60,high dose 2ME2 treatment group(16mg/kg)=60).The normal group was established by intratracheally injected normal saline(5mg/kg)and the other groups of rats were received intratracheal LPS(5mg/kg)to get acute lung injury model.The vehicle group received DMSO intraperitoneal injection of medication,while low dose 2ME2 treatment group and high dose 2ME2 treatment group received injection of 2ME2(8mg/kg or 16mg/kg)and DMSO(16mg/kg)after injection of LPS.2.20 rats of each group were killed at different time point after intratrachealy injection of LPS(3h,9h,24h).Then to observed the level of arterial blood gas?lung water content(lung wet/dry radio)in each time point and each group.Used Elisa method to detect the level of NF-?B?COX-2 in serum.Used the light microscope to obvious the pathological change of the sections of right lung by HE and calculated the the scores of alveolar inflammation.At last,tested the HIF-1? protein expressions by Western Blot,analyzed the correlation of NF-k B andHIF-1? by statistical software.3.Statistical Analysis: All data was expressed as mean ± standard deviation((?)±s),and was analyzed using SPSS22.0 software.P<0.05 means statistical significance.Results:(1)Compared with the normal group,the level of PaO2 in acute lung injury model group and vehicle group significantly decreased,While the lung wet/dry radio ? the lung tissue pathology changes and the scores of alveolar inflammation increased remarkably(P < 0.05).Compared with the vehicle group,the level of PaO2 increased in 2ME2 treatment groups,but the lung wet/dry radio ? lung tissue pathology changes and the scores of alveolar inflammation decreased(P < 0.05).Among the two different dose of 2ME2 treatment groups,the level of PaO2 were higher in high dose group,while the lung wet/dry radio ?lung tissue pathology changes and the scores of alveolar inflammation remarkably were lower in high dose group(P < 0.05).(2)COX-2?NF-?B:The expression of COX-2 ? NF-k B in the normal group were low at different time point.But these were significantly higher in acute lung injury model group and vehicle group induced by LPS(P < 0.05),and arrived with a peak at hour 9.In 2ME2 treat groups,the level of COX-2?NF-?B also rise first and then fall,but compared with the vehicle group,the level of COX-2?NF-?B decreased.Among the two different dose of2ME2 treatment groups,the level of COX-2?NF-?B were lower in high group(P < 0.05).(3)HIF-1? protein: The expression of HIF-1? protein in the normal group show little by western blot.While in acute lung injurymodel group and vehicle group increased at hour 3,arrived with a peak at hour 9.And compared with the vehicle group,the expression of HIF-1? in 2ME2 treatment group decreased(P < 0.05),and in high dose group the expression of HIF-1? protein were lower than in low dose group(P < 0.05).(4)The expression of HIF-1? protein and NF-?B was correlated positively(r=0.995).Conclusion: This study found that in acute lung injury rats induced by LPS,the expression of NF-?B?COX-2 and HIF-1? significantly increased,which might be involved in the formation of acute lung injury.Interestingly,the expression of NF-?B ?COX-2 and HIF-1? decreased after treatment with 2ME2.So,2ME2 might reduce the expression of NF-k B ? COX-2 and HIF-1? to reduce inflammation and relieve acute lung injury. |
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