首页|孕期罗哌卡因麻醉通过NGF/ERK/CREB途径影响SD模型子代情绪及学习记忆能力

孕期罗哌卡因麻醉通过NGF/ERK/CREB途径影响SD模型子代情绪及学习记忆能力

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目的 探讨孕期罗哌卡因麻醉对子代情绪及学习记忆能力的影响及其潜在机制.方法 本研究建立了怀孕大鼠模型,以研究在妊娠中期罗哌卡因麻醉后对后代的神经认知影响.在出生后第几天(P25~30)对其行为进行测试(Morris水迷宫和条件性恐惧实验).此外,通过Nissl染色检测后代的海马形态(P30),并通过Golgi染色测定海马树突棘密度.通过蛋白质印迹法测定海马神经生长因子(NGF)、细胞外信号调节激酶(ERK)、磷酸化ERK(p-ERK),环磷酸腺苷反应元件结合(CREB)、p-CREB、突触素(SYP)、突触蛋白酶(SYN)和突触后密度-95(PSD95)的蛋白水平.此外,SCH772984(ERK抑制剂)用于评估PC12细胞中ERK途径的作用和潜在机制.结果 结果显示罗哌卡因麻醉会导致长期神经认知功能障碍,降低树突旋转的密度,导致神经元损失,并下调海马中NGF、ERK、p-ERK、促分裂原和应激激活蛋白激酶(MSK)、CREB、p-CREB、SYP、SYN和PSD95的表达.结论 在胎儿大脑发育期间,罗哌卡因诱导的母体麻醉会导致后代长期的神经认知功能障碍,这可能是通过抑制海马中的NGF/ERK/CREB通路而发生的.
Ropivacaine anesthesia during pregnancy affects the emotion and learning and memory ability of SD model offspring through NGF/ERK/CREB pathway
Objective To investigate the effect of ropivacaine anesthesia during pregnancy on offspring's emotion and learning and memory ability and its potential mechanism.Methods A pregnant rat model was established to investigate the neurocognitive effects of ropivacaine anesthesia on offspring during the second trimester.The behavior was tested on the first few days after birth(P25-30)(Morris water maze and conditioned fear test).In addition,the hippocampal morphology(P30)of the offspring was detected by Nissl staining,and the density of hippocampal dendritic spines was determined by Golgi staining.Hippocampal nerve growth factor(NGF),extracellular signal-regulated kinase(ERK)and phosphorylated-ERK(p-ERK)were determined by Western blotting.The protein levels of yclic adenosine monophosphate response element-binding(CREB),p-CREB,synaptophysin(SYP),synapsin(SYN)and postsynaptic density-95(PSD95).In addition,SCH772984(an ERK inhibitor)was used to evaluate the role and potential mechanism of the ERK pathway in PC 12 cells.Results The results showed that ropivacaine anesthesia could lead to long-term neurocognitive dysfunction,reduce the density of dendritic rota-tion,lead to neuronal loss,and down-regulate the expression of NGF,ERK,p-ERK,mitogen and stress-activated protein kinase(MSK),CREB,p-CREB,SYP,SYN and PSD95 in hippocampus.Conclusion Ropivacaine-induced maternal anesthesia during fetal brain development can lead to long-term neurocognitive dysfunction in offspring,which may occur by inhibiting the NGF/ERK/CREB pathway in the hippocampus.

ropivacaineNGF/ERK/CREB pathwaypregnancylong-term neurocognitive dysfunction

底妍、焦姗姗、王金保、白喆、张在旺

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中国人民解放军联勤保障部队第九八○医院麻醉科,河北石家庄 050082

罗哌卡因 NGF/ERK/CREB途径 孕期 长期神经认知功能障碍

2020年度河北省医学科学研究课题计划

20200258

2024

中国优生与遗传杂志
中国优生科学协会

中国优生与遗传杂志

CSTPCD
影响因子:0.527
ISSN:1006-9534
年,卷(期):2024.32(8)