右美托咪定对氯胺酮麻醉致幼龄大鼠海马神经元凋亡的影响  

Effect of dexmedetomidine on ketamine anesthesia-induced apoptosis in hippocampal neurons of juvenile rats

作　　者：陈欣[1] 王伟[1] 张建芳[1] 李世勇[1] 杨柳[1] 廖明锋[1] 赵以林[1] 罗爱林[1] 

机构地区：[1]华中科技大学同济医学院同济医院麻醉科,武汉市430030

出　　处：《中华麻醉学杂志》2015年第7期794-797,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81271233）

摘　　要：目的探讨右美托咪定对氯胺酮麻醉致幼龄大鼠海马神经元凋亡的影响。方法清洁级SD大鼠75只，7日龄，体重11～16g，雌雄不拘，采用随机数字表法分为5组（n=15）：对照组（C组）腹腔注射生理盐水0．1ml；氯胺酮麻醉组（K组）腹腔注射氯胺酮50mg／kg；右美托咪定1μg／kg组（Dex1组）、右美托咪定4μg／kg组（Dex：组）和右美托咪定8μg／kg组（Dex，组）腹腔注射氯胺酮和右美托咪定混合液0．1ml，氯胺酮剂量均为50mg／kg，右美托咪定剂量分别为1、4和8μg／kg。于给药结束后3h，翻正反射完全恢复后，放回原笼由相应母鼠喂养；1h后，每组处死5只大鼠，取海马组织，采用Westernblot法检测磷酸化丝氨酸一苏氨酸蛋白激酶（p-Akt）、Akt、活化的caspase-3、caspase-3、Bax、Bcl-2和突触后致密蛋白95（PSD-95）的表达水平。于出生后30d时，每组取10只大鼠，采用Morris水迷宫实验测定空间记忆能力。结果与C组比较，K组第3—5天逃避潜伏期延长，探索时间缩短，海马p-Akt／Akt比值降低，活化的caspase-3／caspase-3比值升高，PSD-95和Bcl-2的表达下调，Bax表达上调（P〈0．05）；与K组比较，Dex1组、Dex2组和Dex3组第3-5天逃避潜伏期缩短，探索时间延长，海马p-Akt／Akt比值升高，活化的caspase-3／caspase-3比值降低，PSD．95和Bcl-2的表达上调，Bax表达下调（P〈0．05）；与Dex1组比较，Dex2组和Dex3组第4、5天逃避潜伏期缩短，探索时间延长（P〈0．05）；Dexl组、Dex2组和Dex，组间海马p-Akt／Akt比值、活化的caspase-3／easpase-3比值、PSD-95、Bax和Bcl-2的表达比较差异无统计学意义（P〉O．05）。结论右美托咪定可通过激活海马Akt，上调PSD．95的表达，减轻氯胺酮麻醉致幼龄大鼠海马神经元凋亡。Objective To investigate the effect of dexmedetomidine on ketamine anesthesia- induced apoptosis in hippocampal neurons of juvenile rats. Methods Seventy-five pathogen-free Sprague- Dawley rats of both sexes, aged 7 days, weighing 11-16 g, were randomly divided into 5 groups （n = 15 each） using a random number table： control group （group C）, ketamine anesthesia group （group K） and dexmedetomidine 1, 4 and 8 μg/kg groups （Dexl, Dex2 and Dex3 groups）. Normal saline 0.1 ml was intraperitoneally injected in group C. Ketamine 50 mg/kg was intraperitoneally injected in group K. A mixture （0.1 ml） of ketamine 50 mg/kg and dexmedetomidine 1, 4 and 8 μg/kg was intraperitoneally injected in Dexl, Dexz and Dex3 groups, respectively. After righting reflex recovered completely, the rats were put back into the cage, and 1 h later 5 rats in each group were sacrificed. Hippocampi were removed for determination of the expression of phosphor-Akt （p-Akt） , Akt, activated caspase-3, caspase-3, Bax, Bcl-2 and post-synaptic density protein 95 （PSD-95） by Western blot. The ratio of p-Akt/Akt and activated caspase-3/caspase-3 were calculated. Ten rats in each group were selected on postnatal day 30 and underwent Morris water maze test 3 times a day for 5 consecutive days. Results Compared with group C, the escape latency was significantly prolonged on 3rd-5th days, the exploration time was shortened, p-Akt/ Akt ratio was decreased, activated caspase-3/caspase-3 ratio was increased, the expression of PSD-95 and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group K. Compared with group K, the escape latency was significantly shortened on 3rd-5th days, the exploration time was prolonged, p- Akt/Akt ratio was increased, activated caspase-3/caspase-3 ratio was decreased, the expression of PSD-95 and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in Dex1, Dex2 and Dex3 groups. The escape latency was significantly shorter on 4th-5th days, and the exploration time w

关 键 词：右美托咪啶 氯胺酮 认知障碍 细胞凋亡 海马 神经元 儿童 

分 类 号：R614[医药卫生—麻醉学]