摘要
氯胺酮是常见的临床麻醉剂,具有较好的镇静、镇痛与麻醉效果。怀孕动物注射氯胺酮是否会影响其子代认知功能仍然未知。本研究通过建立孕鼠暴露模型探究氯胺酮对子代行为学和神经系统的影响。在母鼠怀孕第14天,首先肌肉注射氯胺酮(80 mg/kg),每隔1 h按照40 mg/kg补药3次。子代幼鼠于出生后25~29 d进行Morris水迷宫试验。并应用透射电镜、尼氏染色和高尔基染色确定大脑海马区轴突、尼氏小体和树突棘密度的变化,同时分别通过RT-PCR和Western blot检测海马区离子型谷氨酸受体(GLuN1、GLuN2A、GLuN2B、GluR1和GluR2)、钙/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)、蛋白激酶A(PKA)和蛋白激酶C(PKC)基因的转录和蛋白表达水平。结果表明,氯胺酮麻醉会导致子代幼鼠花费更长的时间找到定位平台,海马区轴突数量、尼氏小体密度和树突棘密度下降,CaMKⅡ、PKA、PKC、GLuN2A、GLuN2B、GluR1和GluR2的蛋白表达显著下降。综上所述,孕鼠长时间氯胺酮麻醉会导致子代幼鼠蛋白激酶和谷氨酸受体发生变化,影响海马体突触可塑性,最终损害学习和记忆能力。
Ketamine is common clinical anesthetic with good sedative,analgesic and anesthetic effects.However,it remains unknown whether ketamine injections in pregnant animals affect cognitive function in their offspring.This study investigated the effects of ketamine on behavior and nervous system of offspring by establishing pregnant rat model.On the 14th day of pregnancy,ketamine(80mg/kg)was injected intramuscularly,and repeated at 40mg/kg three times every hour.The offspring pups were subjected to Morris water maze test from 25th to 29th day after birth.Changes in the density of axons,Nissl bodies and dendritic spines in hippocampus of the brain were determined by transmission electron microscopy,Nissl staining and Golgi staining.Gene and protein expression of ionotropic glutamate receptors(GLuN1,GLuN2A,GLuN2B,GluR1 and GluR2),calcium/calmodulin-dependent protein kinaseⅡ(CaMKⅡ),protein kinase A(PKA)and protein kinase C(PKC)were detected by RT-PCR and Western blot.The results showed that ketamine anesthesia caused offspring pups to take longer to find the positioning platform.Axon number,Nissl body density and dendritic spine density in hippocampus decreased.Protein expressions of CaMKⅡ,PKA,PKC,GLuN2A,GLuN2B,GluR1and GluR2were significantly decreased.In conclusion,prolonged ketamine anesthesia in pregnant rats caused changes in protein kinases and glutamate receptors in offspring pups,affected synaptic plasticity in hippocampus and ultimately impaired learning and memory abilities.
作者
赵菁华
姜胜
张儒新
李沫萱
杨玙
秦潜
高利
曾欢
王巍
宋厚辉
ZHAO Jinghua;JIANG Sheng;ZHANG Ruxin;LI Moxuan;YANG Yu;QIN Qian;GAO Li;ZENG Huan;WANG Wei;SONG Houhui(Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province/Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics&Advanced Technology,College of Animal Science and Technology&College of Veterinary Medicine,Zhejiang A&F University,Hangzhou 311300,China;College of Veterinary Medicine,Northeast Agricultural University,Harbin 150030,China)
出处
《中国兽医学报》
CAS
CSCD
北大核心
2023年第5期1005-1012,共8页
Chinese Journal of Veterinary Science
基金
国家自然科学基金资助项目(32202870,31602119)
浙江农林大学学校科研发展基金资助项目(2021FR005,2022LFR013,2019FR031)
浙江农林大学校级学生科研训练资助项目(S202210341081)
关键词
氯胺酮
妊娠
子代幼鼠
谷氨酸受体
蛋白激酶
ketamine
pregnancy
offspring pups
glutamate receptors
protein kinases
