Effect of nuclear transcription factor-κB(NF-κB)on annexin A2(ANXA2)expression in lipopolysaccharids(LPS)-induced acute lung injury(ALI)in mice with sepsis
Objective To observe the expression of annexin A2(ANXA2)in lung tissues of lipopolysaccha-ride(LPS)-induced acute lung injury(ALI)mice,and to explore the relationship between the expression of ANXA2 and nuclear factor-κB(NF-κB)signaling pathway.Methods 18 healthy male C57BL/6 mice were randomly divided into control group,LPS group and LPS+NF-κB inhibitor group(the following was the inhibitor group),with 6 mice in each group.The mice in the inhibitor group were intraperitoneally in-jected with NF-KB signaling pathway inhibitor ammonium pyrrolidine dithiocarbate(PDTC)50 mg/kg,LPS group and inhibitor group were intraperitoneally injected with LPS 7.5 mg/kg 1 h later,observed for 12 h,blood samples was collected after general anesthesia,and the mice were killed.Lung histopathologi-cal features were observed with HE staining,the middle lobe of the right lung was measured by wet and dry weight,and the ratio of wet and dry weight was calculated.The concentrations of ANXA2 in serum and ANXA2 and TNF-α in the left lung alveolar perfusion fluid were measured by ELISA.The mean of optical density(MOD)of ANXA2,NF-κBp65 and p-NF-KBp65 in lung tissue was determined by immuno-histochemistry,and the relative mRNA expression of NF-κBp65,TNF-α and IL-6 in lung tissue was deter-mined by RT-qPCR.The relative expression levels of ANXA2,NF-κBp65,p-NF-κBp65 and Claudin1 in lung tissues were determined by WB.Results Compared with control group,the lung histopathological injury in LPS group was severe,including necrosis and exfoliation of bronchiolar epithelial cells,thicken-ing of alveolar septum,extravasation of macrophages and lymphocytes in the alveolar cavity and occasional bleeding.In LPS group,compared with control group,the ratio of wet/dry weight in the middle lobe of right lung,the concentration levels of ANXA2 in serum and ANXA2 and TNF-α in alveolar perfusion flu-id,the relative mRNA expression levels of NF-KBp65,TNF-α and IL-6 in lung tissue,the protein MOD values of ANXA2,NF-KBp65 and p-NF-KBp65 and their relative expression levels in lung tissues were sig-nificantly increased(P＜0.05);While the relative expression of Claudin1 protein in lung tissues was sig-nificantly decreased(P＜0.05).Compared with LPS group,the above observation indexes in inhibitor group were significantly improved(P＜0.05).Conclusion NF-κB signaling pathway regulates ANXA2 expression in LPS-induced mouse sepsis associated ALI lung tissue.
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