不同剂量右美托咪定对创伤性脑损伤小鼠急性期脑水肿的影响

发布时间：2018-01-28 22:55

本文关键词： 右美托咪定创伤性脑损伤脑水肿水通道蛋白核因子-κB　出处：《临床麻醉学杂志》2017年12期 　论文类型：期刊论文

【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(P0.01)。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(P0.05或P0.01);D60组上述指标改变较D20组更为明显(P0.05或P0.01)。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。
[Abstract]:Objective to investigate the effects of different doses of dexmetomidine on traumatic brain injury. Methods 132 healthy adult male C57BL / 6J mice were randomly divided into six groups: normal control group (C group) and sham group (sham group). Traumatic brain injury group (TBI group), dexmetomidine 20 渭 g / kg group (D20 group) and D40 group (D40 渭 g / kg) group (60 渭 g / kg group). 22 rats in each group were treated with electronic controlled cerebral cortex impactor (ECCI) to establish TBI mouse model, and 60 渭 g / kg of dexmetomidine 20 渭 g / kg was injected intraperitoneally immediately. The cerebral water content was measured by dry / wet weight method 24 hours after injury and the morphological changes of cortical cells were observed by HE staining. The protein contents of aquaporin 4 (AQP4) and nuclear transcription factor 魏 B (NF-魏 B) in injured brain tissue were detected by Western blot method. On the 7th day, modified neurological defect score (mNSSs) was used to evaluate the degree of neurological impairment. The behavioral changes were observed by Morris water maze test on 7 days. Results compared with the Sham group, the mNSS score at different time points was significantly increased and the escape latency was prolonged. The contents of AQP4 and NF- 魏 B protein in the injured cortex were significantly higher than those in the TBI group. The scores of mNSS, escape latency, brain water content, vacuolar degeneration and inflammatory response of the injured cortical cells were significantly decreased in the dexmetomidine groups. The protein content of AQP4 and NF- 魏 B decreased significantly (P0.05 or P0.01). The change of above indexes in D60 group was more obvious than that in D20 group (P0.05 or P0.01). Conclusion dexmetomidine 2060 渭 g / kg can alleviate acute cerebral edema and cognitive impairment after TBI. This effect is more obvious with the increase of dose, which may be related to the decrease of the expression of AQP4 and NF- 魏 B after TBI.
【作者单位】：天津市神经创伤修复重点实验室武警后勤学院附属医院脑科中心;
【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)
【分类号】：R614
【正文快照】： Effects of different doses of dexmedetomidine on acute brain edema in mice with traumatic brain injuryZHANG Nana,CHENG Shixiang,YI Tailong,HUANG Hongjie,ZHANG Sai,YANG Cheng.Tianjin Key Laboratory of Neurotraum Repair,Affiliated Hospital of Logistics Uni

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