摘要
目的探讨不同剂量右美托咪定对创伤性脑损伤(traumatic brain injury,TBI)小鼠急性期脑水肿的影响。方法健康成年雄性C57BL/6J小鼠132只,随机分为六组:正常对照组(C组)、假手术组(Sham组)、创伤性脑损伤组(TBI组)、右美托咪定20μg/kg组(D20组)、40μg/kg组(D40组)、60μg/kg组(D60组),每组22只。应用电子控制性脑皮质撞击仪(eCCI)建立TBI小鼠模型,即刻经腹腔注射不同剂量右美托咪定(20、40、60μg/kg),每隔2小时给药1次,共3次。伤后24h分别采用干/湿重法测定脑含水量,HE染色法观察损伤侧皮质细胞形态变化,Western blot法检测损伤侧脑组织中水通道蛋白4(AQP4)和核转录因子κB(NF-κB)的蛋白含量。并于伤后第1、2、3、7天采用改良神经功能缺陷评分(mNSS)评价其神经功能受损程度,伤后第4、5、6、7天应用Morris水迷宫实验观察其行为学改变。结果与Sham组比较,TBI组不同时点mNSS评分明显升高,逃避潜伏期明显延长,脑含水量明显升高,损伤侧皮质损伤严重,AQP4和NF-κB蛋白含量明显升高(P<0.01)。与TBI组比较,右美托咪定各剂量组mNSS评分明显降低,逃避潜伏期明显缩短,脑含水量明显降低,损伤侧皮质细胞空泡变性和炎症反应有所改善,AQP4和NF-κB蛋白含量明显降低(P<0.05或P<0.01);D60组上述指标改变较D20组更为明显(P<0.05或P<0.01)。结论右美托咪定20~60μg/kg可以减轻TBI后急性脑水肿和认知功能障碍,随着剂量的增高,此作用更为明显,这可能与降低TBI后AQP4和NF-κB表达密切相关。
Objective To explore the effects of different doses of dexmedetomidine on acute brain edema in mice with traumatic brain injury（TBI）.Methods A total of 132 male C57 BL/6 Jmice were randomly divided into six groups：control group（group C）,sham-operation group（group Sham）,traumatic brain injury group（group TBI）,Dex 20μg/kg（group D20）,40μg/kg（group D40）,and 60μg/kg（group D60）,n=22 in each group.The TBI animal model was established by electric controlled cortical impactor（eCCI）,then intraperitoneal injected by the administration of different doses of dexmedetomidine at 0,2 and 4 hafter TBI.Twenty-four hours post-TBI,brain water content was measured by the dry-wet method,histological observation was performed using HE staining,and aquaporin 4（AQP4）and NF-κB expression were detected using Western blot assay,respectively.Then,the modified neurological scale scores（mNSS）on 1,2,3,and 7 dand Morris water maze（MWM）test on 4,5,6 and 7 dpost-TBI were used to evaluate the neurologic deficit of TBI mice.Results After traumatic brain injury,the mNSS scores,the escape latency,the brain water content and the expression of AQP4 and NF-κB increased significantly in group TBI（P〈0.01）.Different doses of dexmedetomidine significantly reduced the mNSS scores,the escape latency,the brain water content and the expression of AQP4 and NF-κB（P〈0.05 or P〈0.01）.And meanwhile dexmedetomidine can lessen neuronal degeneration,and inflammation response.Additionally,the effect was remarkably in group D60 compared with group D20（P〈0.05 or P〈0.01）.Conclusion Dexmedetomidine can lessen brain edema and cognition impairment induced with traumatic brain injury,which is a dose-effect relationship within 20-60μg/kg,and this effect may be related to the downregulation of AQP4 and NF-κB expression.
出处
《临床麻醉学杂志》
CAS
CSCD
北大核心
2017年第12期1202-1206,共5页
Journal of Clinical Anesthesiology
基金
国家自然科学基金(31200809)
天津市临床医学研究中心科技重大专项(15ZXLCSY00040)
天津市重点实验室开放基金(WYKFZ201601)
武警后勤学院附属医院种子基金(FYZ201505)
