右美托咪定对小鼠内毒素急性肺损伤时线粒体动力学的影响  

Effect of dexmedetomidine on mitochondrial dynamics in mice with endotoxin-induced acute lung injury

作　　者：史佳[1] 吴丽丽[1] 张艳芳[1] 杜诗涵 宫丽荣[1] 余剑波[1] Shi Jia;Wu Lili;Zhang Yanfang;Du Shihan;Gong Lirong;Yu Jianbo(Department of Anesthesiology,Tianjin Nankai Hospital Nankai Clinical College of Tianjin Medical University,Tianjin 300100,China)

机构地区：[1]天津医科大学南开临床学院,天津市南开医院麻醉科,300100

出　　处：《中华麻醉学杂志》2019年第9期1139-1142,共4页Chinese Journal of Anesthesiology

基　　金：天津市自然科学基金青年项目(18JCQNJC11000);天津市自然科学基金重点项目(18JCZDJC35400)。

摘　　要：目的评价右美托咪定对小鼠内毒素急性肺损伤时线粒体动力学的影响。方法清洁级健康雄性成年C57BL/6小鼠30只,体重20~25 g,2月龄,采用随机数字表法分为3组(n=10):对照组(C组)、内毒素急性肺损伤组(LPS组)、内毒素急性肺损伤+右美托咪定组(LPS+DEX组)。LPS组与LPS+DEX组经尾静脉注射LPS 10 mg/kg制备小鼠内毒素急性肺损伤模型。LPS+DEX组于注射LPS前30 min时腹腔注射右美托咪定50μg/kg,C组和LPS组给予等容量生理盐水。给予LPS后6 h时处死小鼠取肺组织,光镜下观察病理学结果并进行肺损伤评分,测定活性氧(ROS)水平,Western blot法测定线粒体融合蛋白1(Mfn1)、Mfn2、视神经萎缩蛋白1(OPA1)、动力相关蛋白1(Drp1)和分裂相关蛋白1(Fis1)的表达水平。结果与C组比较,LPS组和LPS+DEX组肺损伤评分和肺组织ROS水平升高,Mfn1、Mfn2、OPA1表达下调,Drp1、Fis1表达上调(P<0.05)。与LPS组比较,LPS+DEX组肺损伤评分和肺组织ROS水平降低,Mfn1、Mfn2、OPA1表达上调,Drp1、Fis1表达下调(P<0.05)。结论右美托咪定可通过维持线粒体融合/分裂运动平衡,减轻小鼠内毒素急性肺损伤。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 50μg/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.

关 键 词：右美托咪啶 急性肺损伤 内毒素血症 线粒体 

分 类 号：R614[医药卫生—麻醉学]