HMGB1 gene knockout alleviates acute lung injury of sepsis mice via inhibiting TLR4/NF-κB pathway / 安徽医科大学学报

ABSTRACT

Objective To study the effect of high mobility group box B1(HMGB1)gene knockout on alleviating a-cute lung injury and inhibiting toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)pathway of sepsis mice.Methods Wild-type(WT)mice were divided into WT-Sham group and WT-model group,and HMGB1 knockout(KO)mice were divided into KO-sham group and KO-model group.Sepsis ALI model was established by cecal ligation and perforation in WT-model group and KO-model group.Sham operation was performed in WT-Sham group and KO-Sham group.24 h after modeling,the partial pressure of arterial oxygen(PaO2)was detected,oxy-genation index(OI)was calculated,pathological changes of lung tissue were detected and lung injury score was calculated,the concentrations of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),interleukin-6(IL-6),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),in serum and lung tissues and the expression of HMGB1,TLR4 and nuclear NF-κB in lung tissues were detected.Results The PaO2,OI and the concentration of SOD in serum and lung tissue of WT-model group were lower than those of WT-Sham group,the lung injury scores,the concentrations of TNF-α,IL-1 β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of HMGB1,TLR4 and nuclear NF-κB in lung tissue were higher than those in WT-Sham group(P＜0.05).HMGB1 was not expressed in lung tissue of KO-model group,and the concentrations of PaO2,OI and the concentration of SOD in serum and lung tissue of KO-model group were higher than those of WT-model group,the lung injury scores,the concentrations of TNF-α,IL-1β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of TLR4 and nuclear NF-κB in lung tissue were lower than those of the WT-model group(P＜0.05).Conclusion HMGB1 gene knockout alleviates acute lung injury of sepsis mice,the re-lated molecular mechanism may be the inhibition of TLR4/NF-κB pathway mediated inflammation and oxidative stress.