孕中期大鼠氯胺酮麻醉下手术对子代认知功能的影响  

Effect of surgery under ketamine anesthesia during mid-pregnancy on cognitive function of offspring rats

作　　者：冯娜敏 王胜强 曹蒙蒙 刘玉琳[2] 罗佛全[1] 钟宝林[3] 刘志毅[1] 赵伟红[1] Feng Namin;Wang Shengqiang;Cao Mengmeng;Liu Yulin;Luo Foquan;Zhong Baolin;Liu Zhiyi;Zhao Weihong(Department of Anesthesiology, First Affiliated Hospital, Nanchang University, Nanchang 330006, China;Department of Immunology, Medical College of Nanchang University, Nanchang 330006, China;Department of Anesthesiology, Ganzhou People′s Hospital, Ganzhou 341000, China)

机构地区：[1]南昌大学第一附属医院麻醉科,330006 [2]南昌大学基础医学院免疫学教研室,330006 [3]赣州市人民医院麻醉科,341000

出　　处：《中华麻醉学杂志》2019年第1期23-27,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81460175);江西省自然科学基金重点项目(20171ACB20030);南昌大学研究生创新专项资金项目(CX2017221);江西省卫计委中医药科技计划项目(2017A292).

摘　　要：目的评价孕中期大鼠氯胺酮麻醉下手术对子代认知功能的影响。方法妊娠14d健康雌性SD大鼠30只,9~10周龄,体重270~310g,采用随机数字表法分为3组(n=10):氯胺酮麻醉下剖腹探查组(KS组)、氯胺酮麻醉组(K组)和对照组(C组)。KS组经尾静脉注射氯胺酮20mg/kg,当翻正反射消失后以130mg·kg^-1·h^-1的速率持续静脉输注氯胺酮维持麻醉2h,麻醉平稳后行剖腹探查术;K组除不行剖腹探查术外,余处理同KS组;C组注射生理盐水。子代出生后第7、23和30天时分别用悬崖回避实验、避暗实验和Morris水迷宫实验评价空间感知功能和学习记忆功能;水迷宫实验完毕后24h时,取海马组织,采用Q-PCR法测定神经元表达发育下调基因(NEDD9)和突触后致密斑95(PSD-95)的mRNA表达水平,Westernblot法测定NEDD9和PSD-95表达水平。结果与C组比较,KS组悬崖回避实验得分降低,水迷宫实验逃避潜伏期延长,穿越平台次数减少,第2象限停留时间缩短,NEDD9和PSD-95表达水平下降(P<0.05),NEDD9和PSD-95的mRNA表达水平差异无统计学意义,K组上述指标差异无统计学意义(P>0.05);3组避暗实验错误次数比较差异无统计学意义(P>0.05)。结论孕中期大鼠氯胺酮麻醉对子代认知功能无明显影响,氯胺酮麻醉下腹部手术对子代空间感知和学习记忆功能有明显损害,其机制与下调子代海马NEDD9和PSD-95表达有关。Objective To evaluate the effects of surgery under ketamine anesthesia during mid-pregnancy on cognitive function of offspring rats. Methods Thirty healthy pregnant Sprague-Dawley rats at 14 days of gestation, aged 9-10 weeks, weighing 270-310 g, were assigned to 3 groups(n=10 each)using a random number table method: exploratory laparotomy under ketamine anesthesia group(KS group), ketamine anesthesia group(K group)and control group(C group). In KS group, ketamine 20 mg/kg was injected via the caudal vein, and then ketamine was continuously infused at a rate of 130 mg·kg^-1·h^-1 after loss of right reflex to maintain anesthesia for 2 h, and exploratory laparotomy was performed after anesthesia was stable.Group K received no exploratory laparotomy and the other treatments were similar to those previously described in group KS.The equal volume of normal saline was given instead in group C. The cliff avoidance, passive avoidance, and Morris water maze tests were used to evaluate the spatial perception and learning and memory ability of the offspring rats on postnatal days 7, 23 and 30.Hippocampal tissues of rat offsprings were obtained at 24 h after the end of Morris water maze test to determine neural precursor cell-expressed developmentally downregulated protein 9(NEDD9) and postsynaptic density 95(PSD-95)protein and mRNA expression by quantitative polymerase chain reaction or Western blot. Results Compared with group C, the score of cliff avoidance was significantly decreased, the results of Morris water maze test showed that the escape latency was significantly prolonged, the platform-crossing times were decreased, the time spent in the second quadrant was shortened, the expression of NEDD9 and PSD-95 was down-regulated(P<0.05), and no significant changes were found in the expression of NEDD9 and PSD-95 mRNA in KS group, and no significant changes were found in the indexes mentioned above in K group(P>0.05). There was no significant difference in the number of errors in passive avoidance test among the three g

关 键 词：氯胺酮 麻醉 静脉 外科手术 妊娠中期 子代 认知 

分 类 号：R614[医药卫生—麻醉学]