Effect of irisin on ventilator-induced lung injury in rats: relationship with expression of NLRP3 inflammasomes / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of irisin on ventilator-induced lung injury (VILI) in rats and the relationship with expression of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes.Methods:Thirty-six SPF-grade healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 220-300 g, were divided into 3 groups ( n=12 each) using a random number table method: control group (group C), group VILI and irisin group (group I). All the groups underwent tracheotomy and intubation, group C kept spontaneous breathing for 4 h, and the animals were mechanically ventilated for 4 h in VILI and I groups.Irisin 1 μg/kg was injected via the tail vein at 30 min before tracheal intubation in group I, and the equal volume of normal saline mixture (normal saline∶phosphate buffer solution containing 5% trehalose=1∶9) were given in the other 2 groups via the tail vein.The rats were mechanically ventilated with the tidal volume of 20 ml/kg, respiratory rate 80 breaths/min, inspiratory/expiratory ratio 1∶1, inspired oxygen fraction ratio 21% and positive end-expiratory pressure 0.Blood samples from left femoral artery were collected before tracheal intubation and at the end of mechanical ventilation for detection of PaO 2.The animals were sacrificed and the lung tissue samples and bronchoalveolar lavage fluid (BALF) were then collected for examination of the pathological changes (under the light microscope), and for determination of wet to dry weight (W/D) ratio and the concentrations of total protein in BALF and interleukin-1β (IL-1β) and IL-18 in BALF and serum (by enzyme-linked immunosorbent assay), level of reactive oxygen species (ROS) in alveolar macrophages in BALF (by DCFH-DA) and the expression of NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1 protein and mRNA in lung tissues (by Western blot and by quantitative reverse transcription polymerase chain reaction). The pathological changes of the lung were scored. Results:Compared with group C, PaO 2 was significantly decreased at the end of mechanical ventilation, lung injury score and W/D ratio were increased, concentration of total protein and ROS level in alveolar macrophages in BALF and concentrations of BALF, IL-1β and IL-18 in serum were increased, and the expression of NLRP3, ASC and caspase-1 protein and mRNA in lung tissues was up-regulated in group VILI and group I ( P<0.01). Compared with group VILI, PaO 2 was significantly increased at the end of mechanical ventilation, lung injury score and W/D ratio were decreased, concentration of total protein and ROS level in alveolar macrophages in BALF and concentrations of BALF, IL-1β and IL-18 in serum were decreased, and the expression of NLRP3, ASC and caspase-1 protein and mRNA in lung tissues was down-regulated in group I ( P<0.05). Conclusion:Irisin can reduce VILI, and the mechanism is related to inhibiting activation of NLRP3 inflammasome and reducing inflammatory response in rats.