孕晚期七氟烷暴露对子代大鼠脑组织单胺类

Effects of gestational exposure to sevoflurane on expression levels of monoamine neurotransmitters in various brain areas of rat offspring

关键词:  七氟烷  孕期  子代  去甲肾上腺素  多巴胺  五羟色胺

Key words:  sevoflurane  gestation  offspring  norepinephrine  dopamine  -hydroxytryptamine

摘要:

目的　探讨孕晚期七氟烷暴露对子代大鼠脑组织单胺类神经递质含量的影响。 方法8只SD孕大鼠，随机分为3组，对照组、低浓度暴露组和高浓度暴露组，每组6只。孕14 d行麻醉干预，低浓度和高浓度暴露组孕鼠于麻醉箱内分别吸入混有5%和5%七氟烷的空气2 h，对照组吸入空气2 h。测定5周龄子鼠体重、脑重，计算脑脏器系数；水迷宫测试5周龄子鼠学习记忆能力；高效液相色谱-荧光检测法测定5周龄子鼠大脑皮质和海马去甲肾上腺素（norepinephrine，NE）、多巴胺（dopamine，DA）和五羟色胺（5-hydroxytryptamine，5-HT）含量。结果　高浓度暴露组子鼠脑脏器系数（51±0.08）显著低于对照组（63±0.12），P<0.05；定向航行实验训练第1天，各组子鼠游泳速度无明显差异(P>0.05）；从训练第2天起，随暴露浓度增加，子鼠逃避潜伏期逐渐延长(P<0.05）；空间探索实验中，子鼠在目标象限停留时间随暴露浓度增加逐渐缩短(P<0.05）；子鼠大脑皮层NE和5-HT含量随染毒剂量增加逐渐下降(P<0.05）；高浓度暴露组子鼠大脑皮层DA含量也显著低于对照组和低浓度暴露组(P<0.05）；子鼠海马NE和DA含量随染毒剂量增加逐渐下降(P<0.05）；高浓度暴露组子鼠海马5-HT含量也显著低于对照组(P<0.05）。结论　孕晚期七氟烷暴露可导致子代生后成年早期学习记忆能力下降；对脑形态和不同脑区单胺类神经递质含量的影响可能参与其导致的神经发育毒性过程。

Abstract:

Objective To investigate the effects on levels of monoamine neurotransmitters in various brain regions of rat offspring under exposure to sevoflurane during pregnancy.Methods Eighteen pregnant SD rats were randomly divided into groups and treated with 0%，5% and.5% sevoflurane for h on4th gestational day.After delivery，at the age of weeks，body and brain weight of offspring were measured and brain organ coefficient was calculated; learning and memory ability was tested by the Morris water maze (MWM) tests; the levels of norepinephrine (NE)，dopamine (DA) and-hydroxytryptamine (5-HT) in cerebral cortex and hippocampus of offspring were detected.Results The brain organ coefficient in high-level exposed group (51±0.08) was significantly lower than that of the control(63±0.12) (P<0.05).On the first day of training，there was no significant difference in swimming velocity among the groups (P>0.05).From the second day，the escape latency was longer consistently in two exposed groups than the control (P<0.05).In the probe test，the time spent in target quadrant where the platform had been located during training was decreased with sevoflurane-treatment level in a dose-dependent manner (P<0.05).The levels of NE and-HT in offspring cerebral cortex decreased with sevoflurane-treatment level in a dose-dependent manner (P<0.05).The level of DA in offspring cerebral cortex of the high-level exposed group was significantly lower than that of other groups (P<0.05).The levels of NE and DA in offspring hippocampus decreased with sevoflurane-treatment level in a dose-dependent manner (P<0.05) The levels of-HT in offspring hippocampus of the high-level exposed group was significantly lower than that of the control (P<0.05).Conclusion Gestational exposure to sevoflurane resulted in learning and memory impairment at early adulthood.Damaging brain morphology and disturbing levels of monoamine neurotransmitters in brain tissues could occur during the neurodevelopmental toxicity.