艾司氯胺酮减轻大鼠骨骼肌缺血再灌注损伤  

Esketamine reduces ischemia-reperfusion injury of skeletal muscle of rats

作　　者：袁培根[1] 陈顺利[1] 单鸳露[1] 薛彬彬[1] 叶玉柱 林丽娜[1] YUAN Peigen;CHEN Shunli;SHAN Yuanlu;XUE Binbin;YE Yuzhu;LIN Lina(Department of Anesthesiology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第一医院麻醉科,浙江温州325000

出　　处：《基础医学与临床》2023年第12期1822-1826,共5页Basic and Clinical Medicine

基　　金：温州市科技计划项目(Y2020777)。

摘　　要：目的观察低剂量艾司氯胺酮(ESK)预处理对于肢体缺血再灌注损伤(LI/R)的作用。方法对大鼠进行如下分组:sham组(即假手术组)、I/R组(即缺血再灌注组,对单侧肢体先实施3 h缺血处理,再实施2 h灌注)、ESK组(即ESK预处理组,经腹腔注入ESK,用量是5 mg/kg)。切取部分骨骼肌用于湿干重比检测;经由比色法测定血清内肌酸激酶(CK)、乳酸脱氢酶(LDH)的水平;再对部分骨骼肌行冻存处理(-80℃),用于测定丙二醛(MDA)和超氧化物歧化酶(SOD)及Western blot检测胞核核因子E2相关因子2(Nrf2)、胞质血红素加氧酶(HO-1)蛋白的表达;通过免疫组化染色(IHC),对胞核Nrf2和胞质HO-1蛋白进行检测。结果相较sham组,I/R组湿干比、CK、LDH、MDA、Nrf2和HO-1均上调,SOD下调(P<0.05);相较I/R组,ESK组湿干比、CK、LDH与MDA皆明显降低;而SOD、Nrf2和HO-1明显升高(P<0.05)。结论艾司氯胺酮减轻骨骼肌缺血再灌注损伤,可能是通过提高细胞核内Nrf2水平,增强HO-1蛋白的表达来提升抗氧化的能力。Objective To investigate the role of low dose esketamine in pretreated limb ischemia-reperfusion injury.Methods The rats were divided into sham-operated group(Sham group),ischemia-reperfusion group(I/R group,3 h of ischemia and 2 h of reperfusion),esketamine group(ESK group,ip,5 mg/kg).The plasma concentrations of creatine kinase(CK)and lactate dehydrogenase(LDH)were measured.The wet/dry weight ratio of skeletal muscle was immediately detected.The gastrocnemius muscle was harvested and the level of malondialdehyde(MDA)and superoxide dismutase(SOD)was detected by colorimetric assay.The expression of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)were detected by Western blot and immunohistochemical staining.Results Compared with Sham group,the index of wet/dry weight ratio,MDA,CK,LDH,Nrf2 and HO-1 were all increased,but SOD was decreased in I/R group(P<0.05).Compared with I/R group,the index of wet/dry weight ratio,MDA,CK and LDH were significantly lower,but SOD and Nrf2 and HO-1 were significantly higher in ESK group(P<0.05).Conclusions ESK may increase Nrf2 in the nucleus,thereby increase the HO-1 protein as an antioxidant agent.

关 键 词：艾司氯胺酮 缺血/再灌注损伤 氧化应激 核因子E2相关因子2(Nrf2) 

分 类 号：R364[医药卫生—病理学]