Effect of irisin on pyroptosis in rats with ventilator-induced lung injury / 中华麻醉学杂志

ABSTRACT

Objective:To investigate the effect of irisin on pyroptosis in rats with ventilator-induced lung injury.Methods:Thirty-six healthy clean-grade male Sprague-Dawley rats, weighing 200-250 g, aged 6-8 weeks, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), ventilator-induced lung injury group (group V) and ventilator-induced lung injury plus irisin group (group V+ I). In group V+ I, irisin 1 μg/kg was injected via the tail vein before mechanical ventilation.The animals were mechanically ventilated (tidal volume of 40 ml/kg, respiratory rate 60 breaths/min, inspiratory/expiratory ratio 1∶2, positive end expiratory pressure 0 and inspired oxygen fraction ratio 21%.Blood samples were then taken from the femoral artery for blood gas analysis, and PaO 2 was recorded.Bronchoalveolar lavage fluid (BALF) was collected, the total protein concentrations in BALF were measured, and the concentrations of BALF and serum interleukin-1β (IL-1β) and IL-18 were measure by enzyme-linked immunosorbent assay.The lung tissues were obtained for determination of the pathological changes after HE staining which were scored, wet to dry weight (W/D) ratio, expression of pyroptosis-related proteins N-terminal gasdermin D (GSDMD-N) and caspase-1 protein and mRNA (by Western blot or using real-time polymerase chain reaction). Results:Compared with group C, the lung injury score and W/D ratio were significantly increased, PaO 2 and OI were decreased, the total protein concentrations in BALF, concentrations of IL-1β and IL-18 in BALF and serum were increased, and the expression of caspase-1 and GSDMD-N protein and mRNA was up-regulated in group V ( P<0.01). Compared with group V, the lung injury score and W/D ratio were significantly decreased, PaO 2 and OI were increased, the total protein concentrations in BALF, concentrations of serum IL-1β and IL-18 in BALF and serum were decreased, and the expression of caspase-1 and GSDMD-N protein and mRNA was down-regulated in group V+ I ( P<0.01). Conclusion:The mechanism by which irisin reduces ventilator-induced lung injury is probably related to inhibiting pyroptosis in rats.