Effect of dexmedetomidine on NLRP3 inflammasome activity in mice with ventilator-induced lung injury / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of dexmedetomidine on the activity of nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) inflammasome in ventilator-induced lung injury (VILI) in mice.Methods:Eighty-four male SPF C57BL/6J mice, weighing 25-30 g, aged 2-3 months, were divided into 3 groups ( n=28 each) using a random number table method: control group (C group), VILI group and dexmedetomidine group (D group). The mice were tracheostomized and spontaneous breathing was maintained in group C, while the other mice were tracheostomized and mechanically ventilated for 4 h in VILI and D groups.Dexmedetomidine was infused in a loading dose of 1.0μg/kg for 20 min before intubation followed by continuous infusion of 1.0 μg·kg -1·h -1 for 4 h in group D. Blood samples were taken from the femoral artery for blood gas analysis before intubation and at 1, 2 and 4 h of mechanical ventilation (T 1-4), and PaO 2 was recorded for detection of PaO 2.Eight mice were selected at T 4 and sacrificed, and the broncho-alveolar lavage fluid (BALF) was collected for determination of the concentration of total protein, interleukin-1β (IL-1β) and interleukin-18 (IL-18). The lung tissues were removed for microscopic examination of pathologic changes which were scored and for determination of the wet to dry weight (W/D) ratio, expression of IL-1β and IL-18 mRNA (by real-time polymerase chain reaction), and expression of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 (by Western blot). The other 20 mice in each group were observed for the 24-h survival rate. Results:Compared with group C, PaO 2 at T 3 and T 4 and 24-h survival rate were significantly decreased, and the lung injury score, W/D ratio, and concentrations of total protein, IL-1β, and IL-18 in BALF were increased, and the expression of NLRP3, ASC, caspase-1, IL-1β mRNA and IL-18 mRNA was up-regulated in VILI and D groups ( P<0.05). Compared with group VILI, the 24-h survival rate was significantly increased, the lung injury score, W/D ratio, and concentrations of total protein, IL-1β, and IL-18 in BALF were decreased, and the expression of NLRP3, ASC, caspase-1, IL-1β mRNA and IL-18 mRNA was down-regulated in group D ( P<0.05). Conclusion:The mechanism by which dexmedetomidine attenuates VILI may be related to inhibiting NLRP3 inflammasome activity in mice.