The mechanism of imatinib on the regulation of lipopolysaccharide-induced acute lung injury in mice through the Nrf2/HO-1 signaling pathway
Objective To evaluate the effect of imatinib on the endotoxemia-induced acute lung injury in mice.Methods Sixty SPF male,8-12 weeks,C57BL/6 mice were randomly(random)divided into 4 groups(n=15 each):control group(group C),imatinib group(group Ⅰ),endotoxemia group(group LPS)and imatinib+endotoxemia group(group Ⅰ+LPS).The endotoxemia model of acute lung injury was established.After 24 hours,the mice were sacrificed.The pathological changes of lung tissues were evaluated,the lung injury scores were calculated,and the wet/dry ratios of lung tissues were measured.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in serum.Detection kits were used to analyze the levels of malondialdehyde(MDA),glutathione(GSH),catalase(CAT),superoxide dismutase(SOD)and the ratio of reduced glutathione to oxidized glutathione(GSH/GSSG)in lung tissues;The expression levels of phosphorylated nuclear factor-kappa B(p-NF-κB),nuclear factor-erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in lung tissues were analyzed by western blotting.Results Compared with the group C,the wet/dry(W/D)ratio of lungs[(3.47±0.41)vs.(5.58±0.47)],lung injury scores[(1.25±0.89)vs.(10.25±1.75)],and the levels of TNF-α and IL-6 in serum increased in the group LPS(P＜0.05).The levels of SOD,CAT,GSH and GSH/GSSG decreased,the level of MDA increased,and the expression of p-NF-KB,Nrf2 and HO-1 protein up-regulated(P＜0.05).Compared with the LPS group,the W/D ratio of lungs[(5.58±0.47)vss.(4.62±0.38)]and lung injury scores[(10.25±1.75)vs.(7.00±1.31)]in the I+LPS group decreased(P＜0.05),and the levels of TNF-α and IL-6 in the serum decreased(P＜0.05).In lung tissues,the levels of SOD,CAT,GSH and GSH/GSSG increased(all P＜0.05),the level of MDA decreased(all P＜0.05),the expression of p-NF-κB protein decreased,and the expression of Nrf2 and HO-1 protein increased(P＜0.05).Conclusions Imatinib improves sepsis-induced acute lung injury in mice,and the mechanism of actions behind may be related to the inhibition of oxidative stress.
国家临床重点专科急诊医学科建设项目天津市高层次人才选拔培养工程"青年医学新锐"人才项目天津市卫健委中医中西医结合科研课题Tianjin Highlevel Talent Selection and Training Project"Young Medical New Edge"Talent Project
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