Dexmedetomidine ameliorates ventilator-induced lung injury in rats via up-regulating NLRC3
AIM To observe the effect of dexmedetomidine on the expression of NLR family CARD domain containing-3(NLRC3),a nucleotide oligomeric domain like receptor,in rats with ventilator-associated lung injury(VILI).METHODS A total of 36 SD rats were randomly divided into normal control group,model group,and dexmedetomidine group(n=12 in each group).VILI model were made by mechanical ventilation with a ventilator.The dexmedetomidine group was intravenously injected with dexmedetomidine 5 μg·kg-1 at 20 minutes before VILI,then maintain a dose of 5 μg·kg-1·h-1.The normal control group and model group received continuous intravenous infusion of 0.5 mL·kg-1·h-1 of physiological saline.The pathological results of lung tissue in each group of rats were observed under the light microscope and the wet dry weight ratio of lung tissue was detected.Western blot and qRT-PCR were used to detect of protein and mRNA expression of NLRC3,NLR family pyrin domain containing 3 protein(NLRP3),apoptosis associated speck-like protein containing a CARD domain(ASC),caspase-1,and NF-κB p65.The protein level of IL-1β、IL-18 and IL-33 in serum were detected by ELISA.RESULTS Compared with the normal control group,severe pathological damage in the lung tissue were showed in the model group,the wet to dry weight ratio and IQA of lung tissue increased significantly(P＜0.05).NLRC3 protein and mRNA expression in lung tissue down regulated(P＜0.05),NLRP3,ASC,caspase-1,and NF-κB p65 protein and mRNA upregulated significantly(P＜0.05),and the concentration of IL-1β、IL-18 and IL-33 in serum increased significantly(P＜0.05).Compared with the model group,the pathological damage of lung tissue in the dexmedetomidine group showed reduced,and the wet to dry weight ratio and IQA of lung tissue decreased(P＜0.05),the expression of NLRC3 protein and mRNA in lung tissue increased significantly(P＜0.05),NLRP3,ASC,caspase-1,and NF-κB p65 protein and mRNA downregulated(P＜0.05),the concentrations of IL-1β,IL-18 and IL-33 reduced significantly(P＜0.05).CONCLUSION Dexmedetomidine improves VILI in rats by upregulating the expression of NLRC3 in lung tissue,and its mechanism may be related to the inhibition of NLRP3 inflammasome activation.
dexmedetomidinemechanical ventilationsventilator-induced lung injuryinflammationNLR family,pyrin domain-containing 3 protein
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