右美托咪定对反复缺血/再灌注脑损伤小鼠学习记忆能力的影响  

Effect of dexmedetomidine on learning and memory dysfunction of mice with repeated cerebral ischemia/reperfusion injury

作　　者：王建平[1] 朱永锋[1] 

机构地区：[1]河南省人民医院麻醉科,郑州450003

出　　处：《中华实验外科杂志》2016年第4期997-1000,共4页Chinese Journal of Experimental Surgery

摘　　要：目的 观察右美托咪定（Dex）对反复缺血/再灌注（IR）脑损伤小鼠学习记忆能力的影响.方法 无特定病原体（SPF）级成年C57BL/6J小鼠60只,按照随机数字表法分为4组,每组15只.低剂量Dex组（Dex-L组）和高低剂量Dex组（Dex-H组）小鼠分别经腹腔注射Dex 25、50 μg/kg,30 min后夹闭双侧颈总动脉,IR组小鼠建立反复IR脑损伤模型;假手术组（Sham组）小鼠只分离双侧颈总动脉,但不夹闭.采用Morris水迷宫实验测试小鼠术前及术后的学习记忆能力,随后处死小鼠,留取海马组织并测定其湿/干重比（W/D）和总含水量（TCW）,伊文斯蓝（EB）法检测血脑屏障的通透性,原位缺口末端标记法（IUNEL）检测海马组织细胞凋亡指数（AI）.酶联免疫吸附试验（ELISA）法测定海马组织基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶组织抑制物-1（TIMP-1）含量,计算MMP-9/TIMP-1比值.结果 与Sham组比较,IR组小鼠术后3、7d时的逃避潜伏期[（54.72±8.24）s比（19.29±4.56）s、（46.71±8.59）s比（23.73±5.59）s]及游泳距离[（4 789.51±677.28） mm比（2 122.84±543.83） mm、（4 987.84±884.42） mm比（1 123.93±369.38） mm]均延长（P＜0.05）.与IR组比较,Dex-L和Dex-H组小鼠术后3、7d时的逃避潜伏期[（28.47±7.89）s、（21.84±6.12）s比（54.72±8.24） s;（32.62±6.78）s、（24.62±6.95）s比（46.71±8.59）s]及游泳距离[（2 834.75±554.83） mm、（2 234.75±490.83）mm比（4789.51±677.28） mm;（1 952.62±528.48） mm、（1 140.48±389.81） mm比（4987.84±884.42） mm]均缩短（P＜0.05）.与Sham组比较,IR组小鼠海马组织W/D（4.94±0.67比3.46±0.45）、TCW（3.94±0.76比2.46±0.48）、AI[（35.15 ±7.97）％比（2.89±0.99）％]和脑组织EB含量[（19.3±4.6） μg/g比（10.4±3.1）μg/g]均升高（P＜0.05）.与IR组比较,Dex-L组和Dex-H组小鼠海马组织W/D（4.32±0.54、3.78±0.51比4.94±0.67）、TCW （3.32±0.44、2.78±0.41比3.94±0.Objective To investigate the effect of dexmedetomidine （Dex） on learning and memory dysfunction of mice with repeated cerebral ischemia/reperfusion （IR） injury.Methods Sixty C57BL/6J mice,graded as specific pathogen free （SPF）,were randomly allocated into four groups,15 mice per group.Mice were injected intraperitoneally with Dex at doses of 25 and 50 mg/kg respectively 30 min before ischemia,and then bilateral common carotid arteries were clipped for establishing the model of repeated IR cerebral injury in Dex-L group and Dex-H group.Bilateral common carotid arteries of mice were clipped for establishing the model of repeated IR cerebral injury in IR group.Bilateral common carotid arteries of mice were only isolated but not clipped in Sham group.Learning and memory functions of mice were tested by Morris water maze test before and after surgery.After Morris water maze test,mice were euthanized and hippocampus was excised.The ratio of wet weight/dry weight （W/D） and total content of water （TCW） of the hippocampus were tested.The permeability of blood-brain barrier was determined by Evans blue （EB） method.Apoptosis index （AI） of the hippocampus was determined by terminal dexynucleotidyl transferase （TdT）-mediated dUTP nick end labeling （TUNEL） method.Enzyme-linked immunosorbent assay （ELISA） was used to determine the content of matrix metalloproteinases-9 （MMP-9） and tissue inhibitors of matrix metalloproteinases-1 （TIMP-1） of the hippocampus,and TIMP-1/MMP-9 ratio was calculated.Results Compared to Sham group,the escape latency [（54.72 ± 8.24） s vs.（19.29±4.56） s,（46.71 ±8.59） s vs.（23.73 ±5.59） s] and swimming distance [（4789.51± 677.28） mm vs.（2 122.84 ± 543.83） mm,（4 987.84 ± 884.42） mm vs.（1 123.93 ± 369.38） mm] of mice were prolonged at 3rd and 7th day after surgery （both P 〈 0.05） in IR group.Compared to IR group,the escape latency [（28.47 ±7.89） s,（21.84 ±6.12） s vs.（54.72 ±8.24） s;（32.62 ± 6.78�

关 键 词：右美托咪定 脑缺血 再灌注损伤 脱噬作用 记忆 

分 类 号：R587.102[医药卫生—内分泌]