Effect of parecoxib sodium on phenotypic transformation of alveolar macrophages in a mouse model of ventilator-associated lung injury / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of parecoxib sodium on phenotypic transformation of alveolar macrophages in a mouse model of ventilator-associated lung injury (VALI).Methods:Forty-five SPF healthy adult male C57BL/6J mice, weighing 22-30 g, aged 8-12 weeks, were divided into 3 groups ( n=15 each) using a random number table method: sham operation group (S group), VALI group (V group) and parecoxib sodium group (P group). Lipopolysaccharide 20 ng was intraperitoneally injected, and 2 h later the animals were mechanically ventilated (tidal volume 30 ml/kg, respiratory rate 70 breaths/min, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 21%, positive end-expiratory pressure 0) for 4 h to establish the model of VALI.Parecoxib sodium 30 mg/kg was intravenously injected at 1 h prior to mechanical ventilation in group P. The mice were sacrificed at 4 h of ventilation, the right lung was lavaged and the broncho-alveolar lavage fluid (BALF) was collected for determination of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-α) concentrations (by enzyme-linked immunosorbent assay), expression of inducible nitric oxide synthase (iNOS) and arginase-1(Arg-1) in BALF and expression of phosphorylated Janus kinase 2 (p-JAK2) and phosphorylated signal transduction and transcription activator 3 (p-STAT-3) (by Western blot). The left lung was removed for determination of the wet/dry weight ratio (W/D ratio) and for examination of the pathological changes which were scored. Results:Compared with group S, the lung injury score, W/D ratio, concentrations of IL-6, IL-10 and TNF-α in BALF, and expression of iNOS, Arg-1, p-JAK2 and p-STAT-3 were significantly increased in V and P groups ( P<0.05). Compared with group V, the concentration of IL-10 in BALF and expression of Arg-1, p-JAK2 and p-STAT-3 were significantly increased, and the lung injury score, W/D ratio, concentrations of IL-6 and TNF-α in BALF and expression of iNOS were decreased in group P ( P<0.05). Conclusion:Parecoxib sodium promotes phenotypic transformation of alveolar macrophages from M1 subtype to M2 subtype and inhibits inflammatory responses, thus alleviating VALI, which may be related to activating JAK2/STAT-3 signaling pathway in mice.