七氟醚对新生大鼠前额叶皮层和海马组织NR1、NR2A、NR2B表达及行为学的影响  

Effects of sevoflurane anesthesia on expression of NR1,NR2A,and NR2B in prefrontal cortex and hippocampus and behavior changes of neonatal rats

作　　者：张虓宇 贾丽洁 徐子锋[1] ZHANG Xiaoyu;JIA Lijie;XU Zifeng(The International Peace Maternal and Child Health Hospital Affiliated to Shanghai Jiaotong University,Shanghai 200030,China)

机构地区：[1]上海交通大学医学院附属国际和平妇幼保健院,上海市胚胎源性疾病重点实验室,上海200030

出　　处：《山东医药》2020年第11期21-24,共4页Shandong Medical Journal

基　　金：上海市卫生和计划生育委员会科研课题资助项目(20164Y0263);上海申康医院发展中心临床科技创新项目(SHDC12016225);上海交通大学“转化医学交叉研究基金”青年项目(ZH2018QNA33)。

摘　　要：目的观察七氟醚对新生大鼠发育过程中前额叶皮层和海马组织NMDA受体NR1、NR2A、NR2B表达的影响,并观察其行为学改变。方法将54只新生6日龄雄性SD大鼠随机分为七氟醚组和对照组,每组27只,七氟醚组和对照组在6~8日龄时分别每日吸入2.1%七氟醚、70%O22 h。两组8、21日龄时分别选取7只处死,分离前额叶皮层和海马组织,采用Western blotting法检测NR1、NR2A、NR2B蛋白表达。两组分别于21、28、35日龄时,采用旷场实验记录自发运动次数、刻板样运动次数、运动时间、运动距离;35日龄时进行Y迷宫实验,记录总探索次数和自发交替行为正确率。结果与8日龄时比较,七氟醚组21日龄时前额叶皮层组织NR2A蛋白表达降低、NR2B蛋白表达升高,对照组21日龄时前额叶皮层组织NR2A蛋白表达升高、NR2B蛋白表达降低(P均<0.05)。七氟醚组8、21日龄时前额叶皮层组织NR1、NR2B蛋白表达均高于对照组(P均<0.05),两组8、21日龄时海马组织NR1、NR2A、NR2B蛋白表达均无明显变化(P均>0.05)。两组自发运动次数、刻板样运动次数、运动时间、运动距离均随着日龄的增加而逐渐增加,七氟醚组上述指标均高于同日龄对照组(P均<0.05)。两组总探索次数比较P>0.05,七氟醚组自发交替行为正确率低于对照组(P<0.05)。结论反复七氟醚麻醉对新生大鼠海马组织NMDA受体亚型表达没有显著影响,但会导致新生大鼠发育过程中前额叶皮层NR1、NR2B蛋白表达升高及NR2B向NR2A转变的延迟,并引起大鼠自发活动增加、注意力下降。Objective To investigate the effects of repeated sevoflurane anesthesia on the expression of NMDA receptor subunits NR1,NR2A,and NR2B in the prefrontal cortex and hippocampus and behavior changes of neonatal rats.Methods Fifty four six-day-old male Sprague Dawley rats were randomly allocated into the control group and sevoflurane group.Rats in the sevoflurane group and control group were inhaled 2.1%sevoflurane or 70%oxygen for 2 h everyday from postnatal day 6 to day 8,respectively.Seven rats of each group were sacrificed at 8 and 21 days of age and the protein expression of NR1,NR2A,NR2B in prefrontal cortex and hippocampus were detected with Western blotting.Seven rats were randomly selected in each group and open field test was carried out to detect the spontaneous locomotion on postnatal day 21,28,and 35.Y maze was experimented to test the working memory on postnatal day 35.Results Compared with postnatal day 8,the sevoflurane group had a decreased NR2A protein expression and increased NR2B protein expression in the prefrontal cortex at 21 days of age,while the control group had an increased NR2A protein expression and decreased NR2B protein expression in the prefrontal cortex on postnatal day 21(both P<0.05).On postnatal day 8 and 21,the protein expression of NR1,NR2B was significantly higher in the prefrontal cortex of the sevoflurane group than in the control group(both P<0.05);there was no significant difference in the protein expression of NR1,NR2A or NR2B in the hippocampus between two groups on postnatal day 8 and 21(all P>0.05).The spontaneous activity times,inflexible movement times,movement duration,and movement distance in the open field of the two groups gradually increased with the increase of the age.These indexes of the sevoflurane group increased significantly as compared with those of the control group(all P<0.05).There was no significant difference in the total exploration times in the Y maze between two groups(P>0.05).The correct rate of spontaneous alternation in the Y maze decreased in t

关 键 词：七氟醚 神经发育 NMDA受体 前额叶皮层 海马 行为学 大鼠 

分 类 号：R742.8[医药卫生—神经病学与精神病学]