Abstract: Objective To explore the role of reactive oxygen species (ROS)/NOD-like receptor pyrin domain containing 3 (NLRP3) signaling pathway on alleviated ventilator-induced lung injury (VILI) by saxagliptin in rats. Methods Thirty-six SPF-grade healthy Sprague-Dawley rats aged 6-8 weeks, weighing 240-300 g, according to the random number table method, they were randomly divided into 3 groups (n=12): control (group C), VILI (group V) and VILI + saxagliptin (group S). Mechanical ventilation with high tidal volume for 4 hours to simulate a model of VILI in rats. Before endotracheal intubation, 4 hours after mechanical ventilation in Group V and S, or 4 hours after spontaneous respiration in Group C, femoral arterial blood was collected for arterial blood gas analysis to detect PaO2 and glucose levels. Rats were sacrificed, IL-1β and IL-18 concentrations in serum and BALF were determined by ELISA. The wet weight/dry weight ratio (W/D) , pathologic histology changes of lung tissue and lung injury scores were examined. Protein expression levels of NLRP3, ASC, and caspase-1 were detected by the Western blot. ROS expression levels in lung tissues were determined by DCFHDA fluorescence probe. Results Compared with group C, glucose levels were elevated at the end of mechanical ventilation in group V, PaO2 was decreased after ventilation, W/D ratio, lung injury score, IL-1β and IL-18 concentrations in serum and BALF were increased (P0.01), protein expression levels of NLRP3, ASC, and caspase-1 were up-regulated (P0.05), ROS expression was increased in the lung tissue in group V and group S. Compared with group V, PaO2 was elevated at the end of mechanical ventilation in group S, glucose levels, W/D ratio, lung injury score, IL-1β and IL-18 concentrations were decreased(P0.01), protein expression levels of NLRP3, ASC, and caspase-1 in lung tissues were downregulated (P0.05), ROS expression in the lung tissue was decreased in group S. Conclusion Saxagliptin reduces VILI, and the mechanism may be related to inhibition of ROS/NLRP3 signaling pathway.
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