Effect of dexmedetomidine on pyroptosis during lung ischemia-reperfusion in rats: an in vitro experiment / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of dexmedetomidine on pyroptosis during lung ischemia-reperfusion (I/R) in rats.Methods Adult male Sprague-Dawley rats,weighing 250-320 g,were used in this study.The model of isolated lung perfusion was established using an IL-2 Isolated Perfused Rat or Guinea Pig Lung System after the rats were anesthetized.Thirty lungs in which an ex vivo lung perfusion model was successfully established were divided into 3 groups (n=10 each) by a random number table method:control group (C group),I/R group and dexmedetomidine group (DEX group).The lungs were continuously perfused with K-H solution for 150 min in C group.After 15 min of perfusion,lungs were subjected to 60-min suspension of ventilation and perfusion,followed by 75 min of reperfusion and ventilation to establish the model of lung I/R injury in I/R and DEX groups.In DEX group,dexmedetomidine 10 nmol/L was added to K-H solution at the beginning of reperfusion.Lung tissues were obtained for determina-tion of wet/dry weight ratio (W/D ratio) and for examination of pathological changes (with a light microscope) and ultrastructure (using an electron microscope),and the alveolar damage rate (IAR) was calculated.The expression of pyroptosis-related factors including NOD-like receptor family protein 3 (NLRP3),caspase-1,interleukin-1β (IL-1β),IL-18 and gasdermin D (GSDMD) protein and mRNA was detected by Western blot or by real-time polymerase chain reaction.Results Compared with C group,the W/D ratio and IAR in lung tissues were significantly increased,and the expression of NLRP3,caspase-1,IL-1β,IL-18 and GSDMD protein and mRNA was up-regulated in I/R and DEX groups (P＜0.05).Compared with I/R group,the W/D ratio and IAR in lung tissues were significantly decreased,the expression of NLRP3,caspase-1,IL-1β,IL-18 and GSDMD protein and mRNA was down-regulated (P＜0.05),and the pathological changes were significantly attenuated in DEX group.Conclusion The mechanism by which dexmedetomidine reduces isolated rat lung I/R injury may be related to inhibiting pyroptosis.