Effect of dexmedetomidine on mitochondrial dynamics in mice with endotoxin-induced acute lung injury / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of dexmedetomidine on mitochondrial dynamics in mice with endotoxin-induced acute lung injury (ALI).Methods Thirty clean-grade healthy adult male C57BL/6 mice,weighing 20-25 g,aged 2 months,were divided into 3 groups (n=10 each) using a random number table method:control group (group C),endotoxin-induced ALI group (group LPS) and endotoxin-induced ALI plus dexmedetomidine group (group LPS+DEX).In LPS and LPS+DEX groups,lipopolysaccharide (LPS) 10 mg/kg was injected via the caudal vein to establish the model of endotoxin-induced ALI.In group LPS+DEX,dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before injection of LPS,while the equal volume of normal saline was given instead in C and LPS groups.The mice were sacrificed at 6 h after LPS administration,and lung tissues were obtained for examination of the pathological changes (with a light microscope) which were scored and for determination of the level of reactive oxygen species (ROS) and expression of mitochondrial fusion proteins mitofusin 1 (Mfn1),Mfn2,optic atrophy 1 (OPA1),dynamin-related protein 1 (Drp1) and fission protein 1 (Fis1) (using Western blot).Results Compared with group C,the lung injury scores and ROS level in lung tissues were significantly increased,the expression of Mfn1,Mfn2 and OPA1 was down-regulated,and the expression of Drp1 and Fis1 was up-regulated in LPS and LPS+DEX groups (P＜0.05).Compared with group LPS,the lung injury scores and ROS level in lung tissues were significantly decreased,the expression of Mfn1,Mfn2 and OPA1 was up-regulated,and the expression of Drp1 and Fis1 was down-regulated in group LPS+DEX (P＜ 0.05).Conclusion Dexmedetomidine can reduce endotoxin-induced ALI through maintaining the mitochondrial fusion-fission balance in mice.