The Effect Of Parecoxib Sodium On Alveolar Macrophages In A Model Of “double-hit” Lung Injury

Objective To investigate the effect of parecoxib sodium on alveolar macrophages?AM??in a model of"double-hit"lung injury with mouse receiving mechanical ventilation.Methods Forty-five male C57BL/6J mice,aged 8-12 weeks,weighting 22-30g,were randomly divided into 3 groups?n=15 each group?:sham operation group?S group?,lipopolysaccharide?LPS?+high tidal volume mechanical ventilation lung injury group?M group?,and treatment with parecoxib sodium group?P group?.Lung injury model was induced by intraperitoneal injection of LPS plus mechanical ventilation in group M and P.Group P was intravenously injected with parecoxib sodium?30mg/kg?1 hour before mechanical ventilation.Arterial blood gas analysis was examined after ventilation,wet/dry weight?W/D?ratio of lung tissue was calculated,pathological changes of lung tissue were observed,the concentrations of i NOS,Arg-1,IL-6,IL-10 and TNF-?in alveolar lavage fluid?BALF?were detected by Western blot and ELISA.AM?was selected by flow cytometry and the intracellular Ca²⁺,ROS concentration and cell apoptosis ratio were determined.Western blot was used to observe tyrosine kinase 2?JAK2?,signal transduction and activator of transcription 3?STAT-3?.nuclear factor kappa B?NF-?B?-p65 protein and phosphorylation levels.Results Compared with group M,treatment with parecoxib sodium improved the oxygenation,alleviated the pulmonary edema,attenuated the histopathological features of the lung injury in mice of group P.Compared with group M,M1-type markers i NOS,IL-6,TNF-?and ROS released by AM?in BALF were suppressed in mice of group P.Conversely,treatment with parecoxib sodium increased the M2-type markers Arg-1 and IL-10 in BALF,and inhibited the apoptosis of AM?.Compared with group M,the intracellularconcentration of AM?increased followed by treatment with parecoxib sodium,accompanying with the increase of phosphorylation of JAK2/STAT-3 and inhibition of the p65 protein phosphorylation.Conclusion Parecoxib sodium may promote the transformation of alveola macrophages from M1 to M2 type by activating JAK2/STAT-3 and inhibiting the NF-?B signaling pathway,thereby exerting anti-inflammatory functions and alleviating lung injury in mechanically ventilated mice.