Protective Effects Of N-acetylcysteine On LPS-induced Acute Lung Injury Mice And Its Effect On JNK Signaling Pathway

Objective: To investigate the protective effects of N-acetylcysteine(NAC)intraperitoneal injection on lipopolysaccharide(LPS)-induced acute lung injury(ALI)mice and its mechanism.Methods: Thirty male BALB/c mice were randomly divided into NAC 1 group,NAC 2 group,NAC 3 group,model group and control group.There were 6 mice in each group.Each group was anesthetized with chloral hydrate before intranasal instillation.The mice in the NAC 1,2 and 3 groups were given intraperitoneal injection of NAC 100,200,300 mg/kg.After 0.5 h,the mice were given LPS 10?g by intranasal instillation.The model group mice were given LPS 10?g by intranasal instillation.But the control group were given PBS 50?L by intranasal instillation.The mice all were killed by cervical dislocation 7h after intranasal instillation.The chest cavities of mice were fully exposed,and both lungs were removed.The left lung tissues were fixed by formaldehyde solution for histopathological examination.The upper lobes of right lung tissues were used to determine wet/dry weight ratio(W/D).The middle lobes of right lung tissues were used to detect myeloperoxidae(MPO)activity by turbidimetric inhibition immuno assay and the content of tumor necrosis factor-?(TNF-?)and vascular cell adhesion molecule-1(VCAM-1)by enzyme-linked immuno sorbent assay(ELISA).The lower lobes of right lung tissues were used to detect phosphorylated c-Jun N-terminal protein kinase(pJNK)by Western blotting.Results: In the control group,lung tissue structures were clear,alveolar wall structures were complete,pulmonary alveolus intervals were not broadened,and a small number of infiltrations of inflammatory cells were observed.Compared with the control group,the alveolar walls were severely damaged,pulmonary alveolar intervals were broadened,and a large number of infiltrations of inflammatory cells were observed in model group.NAC pretreatment reduced the lung tissue damage in turn with the increase of dose.In the NAC 3 group,the alveolar walls mostly were intact under the light microscope.Compared with the model group,the alveolar septa were significantly narrowed,and the infiltrations of inflammatory cells in the lung tissue were significantly reduced in the NAC 3 group.Compared with the control group,the lung tissue W/D ratio in the model group was increased(P<0.001).Compared with the control group,the lung tissue W/D ratio in NAC 1,2 and 3 groups were increased(all P<0.05).Compared with the model group,the lung tissue W/D ratios in NAC 1,2 and 3 groups were decreased((all P<0.05),indicating NAC pretreatment reduced the lung tissue W/D ratio in LPS induced ALI mice.Compared with the control group,the MPO content of lung tissue was increased in the model group(P<0.001).Compared with the control group,the MPO activity of lung tissue in NAC 1,2 and 3 groups were increased(all P<0.001).Compared with the model group,the MPO activity of lung tissue in NAC 1,2 and 3 group were decreased(all P<0.001),indicating that NAC pretreatment reduced MPO activity of lung tissue in LPS induced ALI mice.Compared with the control group,the TNF-? content of lung tissue was increased in the model group(P<0.001).Compared with the control group,the TNF-? content activity of lung tissue in NAC 1,2 and 3 groups were increased(all P<0.001).Compared with the model group,the TNF-? content of lung tissue in NAC 1,2 and 3 group were decreased(all P<0.05),indicating that NAC pretreatment reduced the expression of TNF-? of lung tissue in LPS induced ALI mice.Compared with the control group,the VCAM-1 content of lung tissue was increased in the model group(P<0.001).Compared with the control group,the VCAM-1 content of lung tissue in NAC 1,2 and 3 groups were increased(all P<0.05).Compared with the model group,the VCAM-1 content of lung tissue in NAC 1,2 and 3 groups were decreased(all P<0.001),indicating that NAC pretreatment reduced the expression of VCAM-1 of lung tissue in LPS induced ALI mice.Compared with the control group,the expression of pJNK protein of lung tissue was increased in the model group(P<0.001).Compared with the control group,the expression of pJNK protein of lung tissue in NAC 1,2 and 3 groups were increased(all P<0.001).Compared with the model group,the expression of pJNK protein of lung tissue in NAC 1,2 and 3 groups were decreased(all P<0.001).Moreover,pairwise comparison between NAC1,2 and 3 group showed all P<0.05,indicating that NAC pretreatment reduced the expression of pJNK protein of lung tissue in LPS induced ALI mice.Conclusions:1.NAC can play an effective protective role by reducing LPS-induced pulmonary edema,lung tissue neutrophilic infiltration and lung tissue TNF-? and VCAM-1 contents in LPS induced ALI mice.2.NAC can inhibite the activation of the JNK signaling pathway in LPS induced ALI mice.3.NAC can exert its anti-inflammatory action on LPS induced ALI,possibly by inhibiting the activation of JNK signaling pathway.