右美托咪定对利多卡因诱发大鼠脊髓神经毒性时BDNF表达的影响  

Effect of dexmedetomidine on BDNF expression during lidocaine-induced spinal neurotoxicity in rats

作　　者：徐海平[1] 赵柏松[1] 佘应军[1] 宋兴荣[1] 

机构地区：[1]广州医科大学附属广州市妇女儿童医疗中心麻醉科,510623

出　　处：《中华麻醉学杂志》2016年第10期1197-1201,共5页Chinese Journal of Anesthesiology

基　　金：广东省自然科学基金（2014A030313648）

摘　　要：目的评价右美托咪定对利多卡因诱发大鼠脊髓神经毒性时脑源性神经营养因子（BDNF）表达的影响。方法雄性SD大鼠56只，体重250-280g，2—3月龄，采用随机数字表法分为7组（n=8）：假手术组（s组）、利多卡因组（L组）、生理盐水对照组（NS组）、不同剂量右美托咪定组（D1组、D2组和D3组）和α2肾上腺素能受体拮抗剂育亨宾组（Y组）。除s组外，其他6组均鞘内注射10％利多卡因20μl；D1组、D2组和D3组注射利多卡因前30min时分别腹腔注射右美托咪定5、15、25μg／kg；Y组注射右美托咪定25μg／kg前15min时腹腔注射育亨宾1．0mg／kg。分别于鞘内给药前和给药后24、48、72h（T1-4）时进行BBB评分和测定热甩尾潜伏期（TFL），以评价运动功能。取脊髓，光学显微镜下观察病理学结果，测定BDNF表达和细胞凋亡情况，计算细胞凋亡指数。结果与S组比较，L组、NS组、D1组、D2组和D3组T2-4时BBB评分降低，TFL延长，脊髓BDNF表达上调，细胞凋亡指数升高（P〈0．05）；与L组比较，D3组T2-4时BBB评分升高，TFL缩短，脊髓BDNF表达上调，细胞凋亡指数降低（P〈0．05），Ns组、D1组、D2组和Y组比较差异无统计学意义（P〉0．05）；与D3组比较，Y组T2-4时BBB评分降低，TFL延长，脊髓BDNF表达下调，细胞凋亡指数升高（P〈0．05）。D3组脊髓病理学损伤明显轻于L组，Y组和L组脊髓病理学结果无明显差异。结论右美托咪定减轻利多卡因诱发大鼠脊髓神经毒性的机制可能与上调BDNF表达有关，其上调BDNF表达的机制全部与激活α2肾上腺素能受体有关。Objective To evaluate the effect of dexmedetomidine on the expression of brain-derived neurotrophie factor （BDNF） during lidocaine-induced spinal neurotoxicity in rats. Methods Fifty-six male Sprague-Dawley rats, weighing250-280 g, aged 2-3 months, were divided into 7 groups （n= 8 each） using a random number table： sham operation group （ group S） , lidocaine group （ group L） , normal saline group （group NS） , 3 different doses of dexmedetomidine groups （D1, D2 and D3 groups） , and α2-adreno- ceptor antagon,ist yohimbine group （group Y）. An epidural catheter was placed at L5,6 interspace. Ten per- cent lidocaine 20 μl was injected intrathecally in all groups except group S. Dexmedetomidine 5, 15 and 25 μg/kg were injected intraperitoneally at 30 min before lidocaine injection in D1, D2 and D3 groups, respec- tively. In group Y, yohimbine 1.0 mg/kg was injected intraperitoneally at 15 min before dexmedetomidine 25 μg/kg was injected. Before intrathecal administration and at 24, 48 and 72 h after intrathecal adminis- tration （T1-4）, the Basso, Beattie, Bresnahan （BBB） Locomotor Rating Scale was used, and the tail flick latency to a thermal nociceptive stimulus （TFL） was measured to assess the locomotor function. The rats were sacrificed after the last behavioral test, and the lumbar segments （ L3-5 ） of the spinal cord were re-moved for pathological examination and for determination of BDNF expression and cell apoptosis. The apop- tosis index was calculated. Results Compared with group S, the BBB score was significantly decreased at T2.4, the TFL was prolonged, the BDNF expression was up-regulated, and apoptosis index was increased in L, NS, D1, D2 and D3 groups （P〈0.05）. Compared with group L, the BBB score was significantly increased at T2-4 , the TFL was shortened, the BDNF expression was up-regulated, and apoptosis index was decreased in group D3 （P〈0.05） , and no significant change was found in the parameters mentioned above in NS, D1, D2 and Y group

关 键 词：右美托咪啶 利多卡因 脊髓 药物毒性 脑源性神经营养因子 

分 类 号：R614[医药卫生—麻醉学]