摘要
目的探讨右美托咪定对创伤性脑损伤大鼠海马神经元自噬的影响。方法健康雄性sD大鼠240只，12～16周龄，体重340～370g，采用随机数字表法分为3组（n=80）：假手术组（S组）、创伤性脑损伤组（TBI组）和右美托咪定组（Dex组）。采用改良自由落体装置制备创伤性脑损伤模型。Dex组于模型制备后即刻腹腔注射右美托咪定15μg／kg。于模型制备后24和48h时进行神经功能缺陷（NDS）评分和Morris水迷宫实验；取脑组织，测定脑水含量。于模型制备后6、12、24和48h时，采用Westernblot法测定海马LC3Ⅱ的表达水平。结果与S组比较，TBI组模型制备后24和48h时脑水含量和NDS评分升高，逃避潜伏期延长，模型制备后6、12、24和48h时海马LC3Ⅱ表达上调（P〈0．05）；与TBI组比较，Dex组模型制备后24和48h时脑水含量和NDS评分降低，模型制备后48h时逃避潜伏期缩短，模型制备后6、12、24h和48时海马LC3Ⅱ表达下调（P〈0．05）。结论右美托咪定减轻大鼠创伤性脑损伤的机制可能与抑制海马神经元自噬有关。
Objective To evaluate the effect of dexmedetomidine on autophagy in the hippocampal neurons of rats with traumatic brain injury （TBI）. Methods Adult male Sprague-Dawley rats, aged 12- 16 weeks, weighing 340-370 g, were randomly divided into 3 groups （n= 80 each） using a random num- ber table： sham operation group （group S）, traumatic brain injury group （group TBI） and dcxmedetomi- dine group （group Dex）. The rats were subjected to a diffuse cortical impact injury caused by a modified weight-drop device to induce TBI. Dexmedetomidine 15 μg/kg was injected intravenously immediately after TBI in Dex group. At 24 and 48 h after TBI, neurological deficit score （NDS） was assessed, Morris water maze test was performed, and brains were removed for detection of brain water content in the brain tissue. At 6, 12, 24 and 48 h after TBI, the expression of hippocampal LC3 Ⅱ was determined using Western blot analysis. Results Compared with group S, brain water content and NDS were significantly increased at 24 and 48 h after TBI, the escape latency was prolonged, and the expression of hippocampal LC3 Ⅱ was up- regulated at 6, 12, 24 and 48 h after TBI in TBI group. Compared with TBI group, brain water content and NDS were significantly decreased at 24 and 48 h after TBI, the escape latency was shortened, and the expression of hippocampal LC3 Ⅱ was down-regulated at 6, 12, 24 and 48 h after TBI in Dex group. Con- clusion The mechanism by which dexmedetomidine reduces TBI is related to inhibition of autophagy in the hippocampal neurons of rats.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2015年第3期373-376,共4页
Chinese Journal of Anesthesiology
