右美托咪定对肠缺血再灌注小鼠TXNIP/ASK1信号通路的影响  

Effect of dexmedetomidine on TXNIP/ASK1 signaling pathway in a mouse model of intestinal ischemia-reperfusion

作　　者：冷玉芳[1,2] 李晓曦 张健民 陈凤 石亚静 刘永强 Leng Yufang;Li Xiaoxi;Zhang Jianmin;Chen Feng;Shi Yajing;Liu Yongqiang(The First Clinical Medical College of Lanzhou University,Lanzhou 730000,China;Department of Anesthesiology,The First Hospital of Lanzhou University,Lanzhou 730000,China)

机构地区：[1]兰州大学第一临床医学院,兰州730000 [2]兰州大学第一医院麻醉科,兰州730000

出　　处：《中华麻醉学杂志》2023年第4期445-449,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81960345);兰州大学医学教育创新发展项目(lzuyxcx-2022-108)。

摘　　要：目的评价右美托咪定对肠缺血再灌注小鼠硫氧还蛋白相互作用蛋白(TXNIP)/细胞凋亡信号调节激酶1(ASK1)信号通路的影响。方法SPF级健康成年雄性C57BL/6J小鼠32只,8~10周龄,体质量18~22 g,采用随机数字表法分为4组(n=8):假手术组(Sham组)、肠缺血再灌注组(I/R组)、TXNIP抑制剂白藜芦醇组(Res组)和右美托咪定组(Dex组)。采用夹闭肠系膜上动脉45 min后恢复灌注120 min的方法制备小鼠肠缺血再灌注损伤模型。Res组小鼠造模前腹腔注射白藜芦醇30 mg/kg,Dex组小鼠于缺血前30 min腹腔注射右美托咪定25μg/kg。于再灌注120 min时,心脏穿刺法采集小鼠血标本,随后处死小鼠取小肠组织,光镜下观察病理学结果并行Chiu评分;采用ELISA法检测血清二胺氧化酶(DAO)浓度;采用Western blot法检测小肠组织TXNIP、ASK1和cleaved-caspase-3的表达水平。结果与Sham比较,I/R组Chiu评分、血清DAO浓度和肠黏膜上皮细胞凋亡率升高,TXNIP、ASK-1和cleaved-caspase-3表达上调(P<0.05);与I/R组比较,Res组Chiu评分、血清DAO浓度和肠黏膜上皮细胞凋亡率降低,TXNIP、ASK-1和cleaved-caspase-3表达下调(P<0.05);与I/R组比较,Dex组Chiu评分、血清DAO浓度和肠黏膜上皮细胞凋亡率降低,TXNIP、ASK-1和cleaved-caspase-3表达下调(P<0.05)。结论右美托咪定减轻小鼠肠缺血再灌注损伤的机制可能与抑制TXNIP/ASK1信号通路,减少细胞凋亡有关。Objective To evaluate the effect of dexmedetomidine on the thioredoxin-interacting protein(TXNIP)/apoptosis signal-regulated kinase 1(ASK1)signaling pathway in a mouse model of intestinal ischemia-reperfusion(I/R).Methods Thirty-two SPF healthy adult male C57BL/6J mice,aged 8-10 weeks,weighing 18-22 g,were divided into 4 groups(n=8 each)using a random number table method:sham operation group(Sham group),intestinal I/R group(I/R group),TXNIP inhibitor resveratrol group(Res group)and dexmedetomidine group(Dex group).The mouse model of intestinal I/R injury was developed by clamping the superior mesenteric artery for 45 min followed by 120-min reperfusion in anesthetized animals.Resveratrol 30 mg/kg was intraperitoneally injected before developing the model in Res group,and dexmedetomidine 25μg/kg was intraperitoneally injected at 30 min before ischemia in Dex group.Blood samples were collected by cardiac puncture at the end of 120-min reperfusion,then the mice were sacrificed,and the small intestine tissues were removed for microscopic examination and for determination of the serum diamine oxidase(DAO)concentration(by enzyme-linked immunosorbent assay)and expression of TXNIP,ASK1 and cleaved-caspase-3 in small intestinal tissues(by Western blot).The apoptosis rate of intestinal epithelial cells was calculated.The intestinal damage was assessed and scored according to Chiu.Results Compared with group Sham,the Chiu′s score,serum DAO concentrations and apoptosis rate of intestinal epithelial cells were significantly increased,and the expression of TXNIP,ASK-1 and cleaved-caspase-3 was up-regulated in group I/R(P<0.05).Compared with group I/R,the Chiu′s score,serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased,and the expression of TXNIP,ASK-1 and cleaved-caspase-3 was down-regulated in group Res(P<0.05).Compared with I/R group,the Chiu′s score,serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased,and the expressi

关 键 词：右美托咪啶 再灌注损伤 肠 硫氧还蛋白质类 MAP激酶激酶激酶5 

分 类 号：R614[医药卫生—麻醉学]