17β-雌二醇对氯胺酮致发育期大鼠远期学习记忆损伤的影响  

Effect of 17β-estradiol on ketamine-induced long-term cognitive deficits in developing rats

作　　者：李建立[1] 吴红海[3] 梁巍[2] 薛改[3] 于洋[3] 侯艳宁[3] 

机构地区：[1]河北省人民医院麻醉科,石家庄050051 [2]河北省人民医院小儿外科 [3]白求恩国际和平医院药剂科

出　　处：《中华行为医学与脑科学杂志》2015年第7期584-587,共4页Chinese Journal of Behavioral Medicine and Brain Science

摘　　要：目的探讨17β-雌二醇对氯胺酮所致发育期大鼠远期学习记忆损伤的影响以及机制。方法80只7d龄雄性SD大鼠，随机数字表法分为对照组（C组），溶剂对照组（V组），17β-雌二醇组（E组），氯胺酮组（K组），氯胺酮＋17β-雌二醇组（K＋E组），每组16只。C组连续3d腹腔注射等容量生理盐水，V组连续3d皮下注射等容量麻油，E组连续3d皮下注射600μg·kg^-1 17β-雌二醇，K组连续3d腹腔注射75mg·kg^-1氯胺酮，K＋E组连续3d腹腔注射75mg·kg^-1氯胺酮，皮下注射600μg·kg^-1 17β-雌二醇。各组大鼠饲养至60d时，采用Morris水迷宫观察各组大鼠行为学变化，行为学测试结束后各组取10只大鼠用ELISA法检测大脑皮层乙酰胆碱酯酶（AchE）活性，用碱性羟胺比色法测定乙酰胆碱（Ach）含量。结果定位航行试验，K组大鼠第3，4，5天，逃避潜伏期[（40．26±2．36）S，（30．25±2．20）S，（21．55±2．42）S]与游泳距离[（1019．35±58．13）cm，（811．16±27．58）cm，（598．34±34．74）cm]均较C组显著延长（均P〈0．05），K＋E组逃避潜伏期[（29．46±2．20）S，（24．86±2．14）s，（17．20±1．91）S]与游泳距离[（913．90±41．89）cm，（729．42±31．36）cm，（487．64±18．61）cm）]均较K组显著降低（均P〈0．05）。第6天行空间探索实验，K组第四象限百分比[（24．5±2．7）％]及穿越平台次数[（1．9±0．5）次]均较C组显著降低（均P〈0．05），K＋E组第四象限百分比[（42．3±3．0）％]及穿越平台次数[（3．5±0．5）次]均较K组显著升高（均P〈0．05）。K组AchE活力[（0．69±0．04）U·mg pro^-1]较C组[（0．52±0．06）U·mg pro^-1]显著升高（P〈0．05），K＋E组AchE活力[（0．58±0．12）U·mg pro^-1]较K组显著下降（P〈0．05）。K组Ach含量[（2．59±0．34）mg·g^-1]较C组显著下降（P〈0．05），K＋E组Ach含量[（3．88±0．61）mg·g^-1]Objective To investigate the effect of 17[3-estradiol on ketamine-induced long-term cognitive deficits in neonatal rats. Methods 80 SD male rats aged 7 days were randomly divided into group C, V, E, K and K＋E, and 16 per group. Group C was intraperitoneally injected with same volume of saline for three consecutive days, Group V was subcutaneously injected with same volume of sesame oil for three consecutive days,Group E was subcutaneously injected with 600 μg · kg^-1 17β-estradiol for three consecutive days,group K was intraperitoneally injected with 75 mg· kg^-1 ketamine for three consecutive days, group K＋E was intraperitoneally injected with 75 mg · kg^-1 ketamine in combination with 600 μg · kg^-1 17β-estradiol injected subcutaneously for three consecutive days. At 2 months of age,learning and memory abilities were tested with the Morris water maze. After Morris water maze test, ten rats from each group were decapitated and the prefrontal cortex （PFC） was isolated to detect acetyl- choline esterase（AchE） activity with ELISA assay and to measure acetylcholine（Ach） level by hydroxylammonium chloride method. Results The escape latency （（40.26±2.36） s, （30.25±2.20） s, （21.55±2.42） s） and path length （ （ 1019.35±58.13 ） cm, （ 811.16±27.58 ） cm, （598.34±34.74） cm） of group K were more than those of group C on the third, fourth and fifth training days （ all P〈 0.05 ）, while escape latency （ （ 29.46 ± 2.20 ） s, （ 24.86 ± 2.14 ） s, （17.20±1.91）s） and path length（（913.90±41.89）cm,（729.42±31.36） cm,（487.64±31.61）cm） of group K＋E were significantly lower than those of group K（ all P〈0.05 ）. On test day 6, rats were subjected to a probe trial, ratio of time spent in the target quadrant （（24.5±2.7） % ） and the number of crossings over previous platform locations （1.9±0.5） in group K were fewer than those of group C （all P〈0.05 ） ,while ratio of time spent in the target quad- rant （ （ 42.

关 键 词：17Β-雌二醇 氯胺酮 皮层区 MORRIS水迷宫 乙酰胆碱酯酶 乙酰胆碱 

分 类 号：R614[医药卫生—麻醉学]