α2肾上腺素能受体激动剂对缺血再灌注大鼠脑组织NF-κB及炎症因子表达的影响  

Activation of theα2 adrenoceptor inhibits the expression of NF-κB and inflammatory cytokines in the rat brain after ischemia-reperfusion

作　　者：邱永升[1] 魏巍[1] 宗小川 周锐 陈夜茜 王帅[1] 姚东东[2] 贾英萍 QIU Yongsheng;WEI Wei;ZONG Xiaochuan;ZHOU Rui;CHEN Yexi;WANG Shuai;Yao Dongdong;JIA Yingping(Department of Anesthesiology,the Children’s Hospital of Zhengzhou University,Children’s Hospital of Henan Province,Zhengzhou Children’s Hospital,Henan Engineering Research Center of Childhood Neurodevelopment,Zhengzhou 450018,China;Dongdong Yao,Department of Anesthesiology,Brigham and Women’s Hospital,Harvard Medical School,Boston MA02101,USA)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院,郑州儿童医院麻醉科,河南省儿童神经发育工程研究中心,郑州450018 [2]哈佛大学医学院附属布列根和妇女医院,美国马萨诸塞波士顿02101

出　　处：《中国比较医学杂志》2020年第7期104-109,共6页Chinese Journal of Comparative Medicine

基　　金：河南省科技攻关计划项目(182102310440);河南省医学科技攻关计划项目(2018020598);河南省国际联合实验室基金项目(201605-005)。

摘　　要：目的评价α2肾上腺素能受体激动剂右美托咪定对大鼠脑缺血再灌注核因子-κB(NF-κB)、脑组织肿瘤坏死因子-α(TNF-α)及白细胞介素-1β(IL-1β)的影响。方法90只SD雄性大鼠,采用数字表法随机分为3组,每组30只,分别为假手术组(S组)、缺血再灌注对照组(C组)和α2肾上腺素能受体激动剂干预组(D组),每组再根据大鼠伤后的生存时间,随机平均分为5个亚组,每组均为6只,即术后2、6、12、24和48 h 5个亚组。大鼠脑缺血再灌注模型参照改良Longa法制造。S组仅做线栓,不做其他处理。D组栓塞成功后于缺血后2 h拔线,至颈外动脉残端内再灌注,在缺血前30 min经腹腔注射α2-AR激动剂右美托咪定100μg/kg(4μg/mL)。C组给予等体积的0.9%生理盐水。各组大鼠分别在伤后相应时间点断头取脑采用免疫印迹分析测定NF-κB,酶联免疫法测定脑组织中TNF-α及IL-1β水平。在模型制备以后24 h、48 h时,分别取出6只大鼠,将其随机放到一个象限之内,测定逃避潜伏期,即大鼠都面向池壁,记录它们在60 s之内找到平台的时间,如果90 s内大鼠未还未找到平台,则认定逃避潜伏期为90 s,每只大鼠测定5次,并取平均值;在模型制备之后24 h、48 h时,分别取6只大鼠,测试警觉性、反应以及协调运动能力。结果脑组织NF-κB、TNF-α及IL-1β含量S组在伤后2、6、12、24、48 h差异无统计学意义。各时间点组间比较,C组以上指标比S组高(P<0.05),D组比S组高(P<0.05),比C组低(P<0.05)。模型制备后24 h、48 h,C组、D组高于S组的神经功能缺陷评分(P<0.05),逃避潜伏期延长(P<0.05),且D组的评分高于C组(P<0.05)。结论α2肾上腺素能受体激动剂能够抑制大鼠脑缺血再灌注时NF-κB、TNF-α及IL-1β的表达,具有脑保护作用。Objective To investigate the neuroprotective effect of theα2 adrenergic agonist dexmedetomidine in rat brain tissues after traumatic brain injury by assessing expression of nuclear factor kappa B,tumor necrosis factorα(TNF-α),and interleukiN-1β(IL-1β).Methods Male Sprague-Dawley rats were randomly divided into one of three groups:the sham operation group(group S),the cerebral ischemia-reperfusion group(group C),and the dexmedetomidine group(group D).Each of these groups was then subdivided into subgroups of 6 rats each for time points 2,6,12,24,and 48 h.Parietal brain contusions were induced according to a modified Longa method.The rats in group S then underwent a sham operation.For group D,2 h after successful embolization a wire was pulled into the stump of the external carotid artery to simulate ischemia and reperfusion,and 30 min later the rats received an intraperitoneal injection of theα2 adrenergic receptor(α2-AR)agonist dexmedetomidine at a dose of 100μg/kg(4μg/mL).Group C underwent the same procedure as group S,but 0.9%NaCl was injected instead of dexmedetomidine.At each time point,nuclear factor kappa B expression was detected using western blotting,and TNF-αand IL-1βexpression were detected using ELISA.Six rats were selected for scoring of neurological deficits at 24 and 48 hours after model preparation,including test response,alertness,and coordination.Six rats were selected 24 and 48 hours after model preparation and randomly placed facing the wall in one quadrant of a cage with a central platform,and,the time it took to find the platform within 60 s was recorded.If the platform was not found within 90 s,the escape latency was recorded as 90 s.Five times were recorded and the average value was calculated.Results No significant differences in TNF-αand IL-1βexpression in the brain tissue at 6,12,24,and 48 h in group S were found.TNF-αand IL-1βexpression was higher in group C than in group S(P<0.05),higher in group D than in group S(P<0.05),but lower in group D than in group C(P<0.05).At

关 键 词：Α2肾上腺素能受体激动剂 脑缺血再灌注 核因子-ΚB 肿瘤坏死因子-α 白细胞介素-1Β 

分 类 号：R-33[医药卫生]