新生小鼠七氟醚暴露对其青春期记忆及突触可塑性的影响  

Effect of neonatal sevoflurane exposure on memory and synaptic plasticity at puberty in mice

作　　者：王加仑 廉海光 林凤颜 李建[1] Wang Jialun;Lian Haiguang;Lin Fengyan(Dept op Anesthesiology,Hatoo Women's Children's Hospital,Haikoo 570206)

机构地区：[1]海口市妇幼保健院麻醉科,海口570206

出　　处：《安徽医科大学学报》2020年第4期513-517,共5页Acta Universitatis Medicinalis Anhui

基　　金：海南省医学科技攻关计划项目(编号:201704248)。

摘　　要：目的探讨小鼠在新生期七氟醚接触暴露对其青春期记忆和突触可塑性的影响。方法 30只新生小鼠(6~7 d龄)随机分为对照组和七氟醚暴露组,每组15只。对照组新生小鼠不进行七氟醚暴露,七氟醚暴露组新生小鼠采用3.5%七氟醚麻醉30 min,然后用3%七氟醚麻醉30 min,最后用2.5%七氟醚麻醉30 min。在2月龄时,通过Morris水迷宫测试、关联性恐惧与条件恐惧测试和三箱交互行为学测试法分别评估各组小鼠的空间记忆、恐惧记忆和社交记忆;免疫组化检测各组小鼠的海马区半胱氨酸蛋白酶3(Caspase-3)和脑源性神经营养因子(BDNF)水平,采用全细胞膜片钳评价各组小鼠的GABA能神经元微小兴奋性突触后电流(mEPSC)的频率和幅度。结果行为学实验结果显示,与对照组比较,七氟醚暴露组小鼠在2月龄时出现空间记忆、恐惧记忆及社交记忆障碍(P<0.001)。免疫组化结果显示,与对照组比较,七氟醚暴露组小鼠在2月龄时海马区BDNF阳性细胞数明显降低(P<0.001),Caspase-3阳性细胞数明显增高(P<0.001)。全细胞膜片钳结果显示,与对照组比较,七氟醚暴露组小鼠在2月龄时GABA能神经元mEPSC频率和振幅均明显降低(均P<0.01)。结论新生小鼠七氟醚暴露可导致其青春期神经退行性变、记忆障碍和突触可塑性降低。Objective To examine the effect of sevoflurane exposure at the neonatal period on memory and synaptic plasticity at puberty in mice. Methods 30 neonatal mice(6~7 days old) were randomly divided into control group and sevoflurane exposure group, 15 mice in each group. The neonatal mice in the control group were not exposed to sevoflurane. The neonatal mice in the sevoflurane exposure group were anesthetized with 3.5% sevoflurane for 30 min, then with 3% sevoflurane for 30 min, and finally with 2.5% sevoflurane for 30 min. At 2-month-old, spatial memory, fear memory and social interaction memory were evaluated by morris water maze test, contextual fear and cue fear test and triple chambered social behavioral assay, respectively. The levels of Caspase-3 and BDNF in hippocampus were detected by immunohistochemical staining. The frequency and amplitude of mEPSC in GABA-ergic neurons were evaluated by whole cell patch clamp. Results Behavioral experiments show that compared with control group, mice in sevoflurane exposure group showed impairment in spatial memory, fear memory and social interaction memory at 2-month-old(all P<0.001). Immunohistochemistry showed that compared with the control group, the number of BDNF positive cells significantly reduced(P<0.001) while the number of Caspase-3 positive cells significantly increased(P<0.001) in hippocampus of mice in sevoflurane exposure group at 2-month-old. Whole cell patch clamp showed that compared with the control group, the frequency and amplitude of mEPSC significantly reduced(all P<0.01) in GABA-ergic neurons of mice in sevoflurane exposure group at 2-month-old. Conclusion Sevoflurane exposure at the neonatal period in mice can lead to neurodegeneration, memory impairment and synaptic plasticity decrease at puberty.

关 键 词：七氟醚 学习记忆 突触可塑性 

分 类 号：R114[医药卫生—卫生毒理学]