7,8-二羟基黄酮对小鼠新生期七氟烷暴露所致自闭症样行为的影响
Effect of 7,8-dihydroxyflavone on autism-like behavior induced by sevoflurane exposure in neonatal mice
袁谊康 1邬温馨 1彭勉1
作者信息
- 1. 武汉大学中南医院麻醉科 湖北 武汉 430071
- 折叠
摘要
目的:探讨7,8-二羟基黄酮(7,8-DHF)对发育早期反复七氟烷暴露所导致小鼠成年期自闭症样行为的影响.方法:将 74 只 7 日龄SPF级C57BL/6 品系小鼠随机分为对照组(Con组)、七氟烷组(Sev组)、七氟烷+vehicle组(vehicle组)、七氟烷+7,8-DHF(7,8-DHF组).Sev组小鼠7日龄起连续3 d每天暴露于3%七氟烷及30%的氧气中2 h;Con组小鼠仅暴露于30%的氧气中2 h;7,8-DHF组和vehicle组小鼠接受与Sev组相同七氟烷暴露,并在3周后分别腹腔注射5 mg/kg的7,8-DHF或同等体积的溶剂,每天一次,共持续21 d.7周龄时对小鼠进行社交等行为学测试及取材(背侧海马组织).结果:与Con组相比,Sev组小鼠社交新颖性偏好缺陷,自我理毛时间增加,背侧海马组织脑源性神经营养因子(BDNF)蛋白及mRNA表达减少;与vehicle组相比,7,8-DHF组小鼠社交新颖性偏好缺陷和机械样重复性行为得到改善.结论:发育早期重复暴露于七氟烷可导致成年后自闭症样行为和背侧海马BDNF表达降低,7,8-DHF可有效改善新生期七氟烷暴露所致自闭症样行为.
Abstract
Objective:To explore the effect of 7,8-dihydroxyflavone(7,8-DHF)on autism-like behavior in mice induced by repeated exposure to sevoflurane in the early development stage.Methods:Seventy-four 7-day-old SPF C57BL/6 mice were randomly divided into the control group(Con group),sevoflu-rane group(Sev group),sevoflurane+vehicle group(vehicle group),and sevoflurane+7,8-DHF group(7,8-DHF group).At the age of 7 days,mice in the Sev group were exposed to air with 3%sevo-flurane and 30%oxygen for 2 hours per day for 3 consecutive days,while the mice in the Con group were only exposed to 30%oxygen.The mice in the 7,8-DHF group and vehicle group received the same exposure to sevoflurane as the Sev group,and they were intraperitoneally injected with 5 mg/kg of 7,8-DHF or equivalent volume of solvent once a day for 21 days after 3 weeks.Social behavioral tests and sampling of mice(dorsal hippocampal tissue)were performed at the age of 7 weeks.Results:Compared with the Con group,the mice in the Sev group showed a deficiency of social novelty preference,longer self-grooming time,and decreased expression of brain-derived neurotrophic factor(BDNF)protein and mRNA in dorsal hippocampal tissue.Compared with the vehicle group,the social novelty preference defect and mechanical repetitive behavior of the mice in the 7,8-DHF group were im-proved.Conclusion:Repeated exposure to sevoflurane in the early development stage of the mice leads to autism-like behavior and reduces expression of BDNF in the dorsal hippocampus in adulthood.How-ever,7,8-DHF could effectively reverse the disorders caused by neonatal exposure to sevoflurane.
关键词
七氟烷/自闭症/脑源性神经营养因子/7,8-二羟基黄酮Key words
Sevoflurane/Autism/Brain-Derived Neurotrophic Factor/7,8-Dihydroxyflavone引用本文复制引用
基金项目
湖北省医学青年拔尖人才计划(HB20200407)
出版年
2024
NETL
NSTL
万方数据