新生大鼠七氟烷暴露对发育期大脑创伤应激反应的影响与机制研究  

Effect and mechanism of neonatalrats sevoflurane exposure on traumatic stress response of developing brain

作　　者：陈本祯[1] 江利华[2] 李惠玲[2] 张明强 CHEN Ben-zhen;JIANG Li-hua;LI Hui-ling;ZHANG Ming-qiang(Department of Anesthesiology, Sichuan Provincial Women′s and Children′s Hospital, The Affiliated Women′s and Children′s Hospital of Chengdu Medical College, Chengdu 610045,China;Department of Operating Room, Sichuan Academy of Medical Sciences & Sichuan Provincial People′s Hospital, Chengdu 610072, China;Department of Anesthesiology,The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072, China)

机构地区：[1]四川省妇幼保健院麻醉科,四川成都610045 [2]四川省医学科学院·四川省人民医院手术室,四川成都610072 [3]成都中医药大学附属医院麻醉科,四川成都610072

出　　处：《实用医院临床杂志》2022年第3期5-8,共4页Practical Journal of Clinical Medicine

基　　金：四川省卫生健康委员会科研课题(重点研究项目)(编号19ZD009)。

摘　　要：目的探讨新生大鼠七氟烷暴露对发育期大脑创伤应激反应的影响和机制。方法新生期SD雄性大鼠(出生后7天内)36只,随机数字表法分为七氟烷组(SEV组),七氟烷+布美他尼组(SEV+BUM组)和对照组各12只,SEV组和SEV+BUM组在出生后第5、6、7天连续行2.1%七氟烷暴露2小时。对照组大鼠在出生后24、25和26天连续行七氟烷暴露2小时,暴露完成后各取一批次大鼠立即通过RT-PCR分析大脑前额叶皮质中NKCC1和KCC2的mRNA水平,其余批次在生后31~34天(青春期)建立经足电休克创伤应激障碍模型,测试大鼠血清皮质酮水平。结果SEV组大脑前额叶皮层NKCC1/KCC2 mRNA表达比率较对照组显著增加(P<0.01)。SEV组大鼠在创伤后应激障碍模型中血清皮质酮的分泌较对照组明显增加(P<0.01),恐惧消退训练和重现测试中的僵直比例和对照组相比明显增加,差异有统计学意义(P<0.01)。结论新生大鼠七氟烷重复暴露会加重大鼠青春期的创伤后应激障碍,其机制可能与新生儿脑去极化GABAAR活动增强有关。Objective To explore the effect and mechanism of neonatalratssevoflurane exposure on traumatic stress response of developing brain.Methods 36 Neonatal Sprague-Dawley male rats(within 7 days of birth)were randomly divided into a sevoflurane group(SEV group),sevoflurane+bumetanide group(SEV+BUM group)and a control group,12 in each group.The SEV group and SEV+BUM groupwereexposed to 2.1%sevoflurane for 2 hours on the 5th,6th,and 7thday after birth.The control groupisexposed to sevoflurane for 2 hours on the 24th,25th,and 26thday after birth.Immediately after exposure,a batch of rats was taken to analyze the mRNA levels of NKCC1 and KCC2 in the prefrontal cortex(PFC)of the brain by RT-PCR.The rest of the batches were used to establish a model of traumatic stress disorder through foot electrical shock at the 31~34 day after birth(adolescence),and measure the serum corticosterone level of the rats.Results NKCC1/KCC2 mRNA ratio was increased in the of the SEV group compared with the control group(P<0.01).Compared with the control group,the serum corticosterone secretion of the rats in the SEV group was significantly increased in the model of post-traumatic stress disorder(P<0.01).The proportion of rigidity in the fear extinction training and recall test in the SEV group was significantly increased compared with the control group(P<0.01).Conclusion Repeated exposure to sevoflurane in neonatal rats exacerbates post-traumatic stress disorder in rat puberty.The mechanism might be associated with the neonatal enhanced brain depolarizing GABAAR activity.

关 键 词：新生期 七氟烷 创伤后应激障碍 γ-氨基丁酸A型受体 

分 类 号：R34[医药卫生—基础医学]