| Background and Objective:Acute lung injury is the damage of capillary endothelial cells and alveolar epithelial cells caused by various factors,accompanied by lung interstitium edema,alveolar edema,pulmonary inflammatory response and inflammatory damage,progressive aggravated hypoxemia and dyspnea.ALI has the characteristics of high mortality,difficult treatment and poor prognosis.It is still a critical problem to be solved urgently in order to find an effective therapeutic method for ALI.Hydrogen sulfide is the third endogenous gas signaling molecule,which was found after nitric oxide and carbon monoxide.Previous studies have found that in the lung injury caused by limb injury,productionof H2 S in lung tissue and concentration of H2 S in the serum were reduced.NaHS,used as exogenous hydrogen sulfide donor,can reduce lung injury induced by limb injury.A large number of literatures have reported that exogenous H2 S donor can alleviate the lung injury induced by hyperbaric oxygen,LPS,ischemia reperfusion and mechanical ventilation,directing inhalation of hydrogen sulfide gas can also alleviate ALI caused by LPS.However,the mechanisms of pulmonary protection effects of H2 S still remain unknown.In this study,ALI model was established by intratracheal instillation of LPS,the plasma level of H2 S,endothelial progenitor cells,pulmonary macrophages and inflammatory cytokines in ALI mice were detected,and the effects of H2 S on lung injury were observed.To investigate the role of H2 S in EPCs mobilization and re-endothelialization and the association between H2 S and AM phenotype transformation in ALI in order to provide a new solution for the treatment of ALI.Methods:1.Acute lung injury was induced by intratracheal injection of LPS in mice.2.The lung specimens of each group were compared,and the lung pathological changes,lung coefficient and lung histopathological score were measured by optical microscope.3.The concentrations of factors IL-6,IL-8 and TNF-α in plasma at different time points in each group were measured.4.The concentrations of serum H2 S in different time points were measured.5.The expression of CD34+/VEGFR2+ in lung tissue of mice was detected.6.The expression of iNOS and Arginase in lung tissue of mice were detected.Results:1.Acute lung injury model was successfully established: In LPS group,the lung tissue at different time points showed different degrees of damage of capillary epithelium and alveolar wall,the alveolar wall and lung interstitium were markedly thickened,and a large number of red blood cells and inflammatory cells infiltrated in the lung interstitium and alveolar.Compared with Sham group,the lung coefficient and IQA increased significantly.2.In LPS group,hemorrhage in lung of LPS group mice was more severe than that of Sham mices at 3th day post-LPS injection.Lung interstitium thickening,erythrocyte exudation and inflammatory cell infiltration were the most serious at 3th day post-LPS injection.The lung coefficient,IQA and inflammatory reactionon at 3th day post-LPS injection were higher than at 1,5,7th day post-LPS injection.3.IQA and lung coefficient of lung tissue in Na HS group were significantly lower than those in the LPS group.IQA and lung coefficient in PAG group and AOAA group were significantly increased than those in LPS group.4.The level of serum H2 S in ALI mice was significantly decreased.The level of serum H2 S in NaHS group was significantly higher than that in LPS group.5.The number of CD34+/VEGFR2+ cells in lung tissue of NaHS group was significantly higher than that of LPS group.6.The Arginase/iNOS ratio of lung tissue in NaHS group was significantly higher than that in group LPS.Conclusion:1.Intratracheal instillation of LPS could induce lung injury,and this methods used to establish ALI model has the advantages of good repeatability and stability.To provide a stable animal model for further study on the related pathophysiological mechanisms of ALI.2.At 3th day post-LPS injection,the lung injury was the most serious.Therefore,3th day post-LPS injection was chosed to be time points in following study.3.Exogenous H2 S could promote EPCs mobilization and re-endothelialization in the lung,regulate of alveolar macrophage phenotype transformation,alleviate ALI lung injury and improve the prognosis of ALI. |
