右美托咪定减轻七氟烷诱发新生大鼠中枢神经毒性的机制:与脑红蛋白的关系  

Mechanism of dexmedetomidine alleviating sevoflurane-induced neurotoxicity in neonatal rats:relationship with Ngb

作　　者：高艳[1] 王丽[1] 刘辉[1] Gao Yan;Wang Li;Liu Hui(Department of Anesthesiology,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,China)

机构地区：[1]河北北方学院附属第一医院麻醉科,张家口075000

出　　处：《中华麻醉学杂志》2021年第6期695-698,共4页Chinese Journal of Anesthesiology

摘　　要：目的:评价右美托咪定减轻七氟烷诱发新生大鼠中枢神经毒性的机制与脑红蛋白(Ngb)的关系。方法:健康雄性SD大鼠84只,7日龄,体重12~16 g,采用随机数字表法分为4组(n=21):对照组(C组)、七氟烷组(S组)、七氟烷+右美托咪定组(SD组)和七氟烷+右美托咪定+育亨宾组(SDY组)。七氟烷麻醉方法:吸入8%七氟烷麻醉诱导,3%七氟烷麻醉维持4 h。于麻醉结束时,SD组腹腔注射右美托咪定50μg/kg,SDY组腹腔注射右美托咪定50μg/kg后立即腹腔注射α2肾上腺素能受体拮抗剂育亨宾0.5 mg/kg。每组随机选取6只大鼠,于麻醉结束后24 h时处死,取脑组织,采用HE染色法检测海马CA1区病理学结果,采用免疫荧光染色法检测海马区Ngb的表达,采用Western blot法检测Ngb、细胞色素c(Cyt c)和caspase-3表达水平;剩余大鼠在28日龄时行Morris水迷宫实验。结果:与C组比较,S组Ngb、Cyt c和caspase-3表达上调,逃避潜伏期延长(P<0.05),海马CA1区病理学改变加重,Ngb荧光强度增强;与S组比较,SD组Ngb表达上调,Cyt c和caspase-3表达下调,逃避潜伏期缩短(P<0.05),海马CA1区病理学改变减轻,Ngb荧光强度增强;与SD组比较,SDY组Ngb表达下调,Cyt c和caspase-3表达上调,逃避潜伏期延长(P<0.05),海马CA1区病理学改变加重,Ngb荧光强度减弱。结论:右美托咪定减轻七氟烷诱发新生大鼠中枢神经毒性的机制可能与激活α2肾上腺素能受体,上调Ngb表达有关。Objective To evaluate the mechanism of dexmedetomidine alleviating sevoflurane-induced neurotoxicity and the relationship with neuroglobin(Ngb)in neonatal rats.Methods Eighty-four healthy male Sprague-Dawley rats,aged 7 days,weighing 12-16 g,were divided into 4 groups(n=21 each)using a random number table method:control group(group C),sevoflurane group(group S),sevoflurane plus dexmedetomidine group(group SD),and sevoflurane plus dexmedetomidine and yohimbine group(group SDY).Sevoflurane anesthesia method:anesthesia was induced by inhaling 8%sevoflurane and then maintained by inhaling 3%sevoflurane for 4 h.At the end of anesthesia,dexmedetomidine 50μg/kg was intraperitoneally injected in group SD,and 0.5 mg/kg yohimbine(α2 adrenergic receptor antagonist)was intraperitoneally injected immediately after the end of intraperitoneal injection of dexmedetomidine 50μg/kg in group SDY.Six rats were randomly selected from each group and sacrificed at 24 h after the end of anesthesia.The brain tissues were removed for determination of histopathologic changes in hippocampal CA1 region(using HE staining),the expression of Ngb in the area of the hippocampus(by immunofluorescence staining)and the expression of cytochrome C(Cyt c)and caspase-3(by Western blot).The other rats were fed until 28 days old,and Morris water maze test was performed.Results Compared with group C,the expression of Ngb,Cyt c and caspase-3 was significantly up-regulated(P<0.05),histopathologic changes in hippocampal CA1 region were accentuated,and Ngb fluorescence intensity was increased in group S.Compared with group S,the expression of Ngb was significantly up-regulated,expression of Cyt c and caspase-3 was down-regulated,the escape latency was shortened(P<0.05),histopathologic changes in hippocampal CA1 region were reduced,and Ngb fluorescence intensity was increased in group SD.Compared with group SD,the expression of Ngb was significantly down-regulated,expression of Cyt c and caspase-3 was up-regulated,the escape latency was prolonged(P<0.05),his

关 键 词：右美托咪啶 麻醉药 吸入 脑红蛋白 药物毒性 

分 类 号：R614[医药卫生—麻醉学]