多次使用咪达唑仑对小鼠学习记忆、海马CA_1区长时程增强诱发和钙/钙调素依赖性蛋白激酶-Ⅱ的影响  

Change of Learning,Memory ,Induction of Long-Term Potentiation and Levels of CaMKⅡin the Hippocampus after Repeated Midazolam Administration in Mice

作　　者：袁力勇[1] 王义桥 王霞民[1] 戴体俊[2] 程芳[3] 

机构地区：[1]浙江省宁波市妇女儿童医院,315012 [2]徐州医学院江苏省麻醉医学重点实验室 [3]江苏省连云港市东方医院

出　　处：《医学研究杂志》2007年第5期57-60,共4页Journal of Medical Research

基　　金：国家自然科学基金资助项目(39970715;30471657);江苏省自然科学基金资助项目(BK2001143)

摘　　要：目的观察多次使用咪达唑仑(Mid)后对小鼠学习记忆的影响,并探讨其机制。方法60只KM小鼠按分层随机区组设计分成M1、M2、M3、M4和NS组,每组12只。分别腹腔注射0.5mg/kg、1mg/kg、2mg/kg、4mg/kgMid或生理盐水。每天3次,连续10天。第10天给药后30min,进行避暗实验训练,24h后测验。避暗实验测验后各组随机取6只小鼠,取海马分别检测LTP和CaMKⅡ含量(western-blot法)。比较各组小鼠测验时的潜伏期和错误次数、HFS前、60min后PS变化幅度和CaMKII含量。结果各剂量Mid组分别与NS组相比,潜伏期缩短、错误次数增多;在HFS后60min时,M1、M2、M3、M4组和NS组PS幅度分别为刺激前的208.60±8.82%、173.81±10.73%、138.41±8.50%、126.27±10.52%和260.60±48.62%,各剂量Mid组PS变化幅度分别与NS组相比,幅度明显降低(P<0.05);M2、M3和M4组与M1组相比、M3和M4组与M2组相比,潜伏期缩短、错误次数增多;PS变化幅度降低和CaMKⅡ含量减少(P<0.05),似呈剂量依赖性;但M3组与M4组相比,潜伏期和错误次数、PS变化幅度、CaMKⅡ含量均相似(P>0.05)。结论行为学、电生理和生化检测结果相一致,多次使用Mid后可以抑制小鼠的学习记忆,并呈一定的剂量依赖性,但该作用有封顶效应。Mid可能通过抑制CaMKⅡ对学习记忆产生影响。Objective To investigate the effects of repeated midazolam administration on learning and memory,induction of long - term potential（LTP）, levels of calcium/calmodulin - dependent protein kinase - Ⅱ in area CAl of hippocampus in mice. Methods 60 KM mice were divided into 5 groups according stratified random block design： midazolam 0.5 mg/kg （ M1 ） ,midazolam 1mg/kg（ M1 ） , midazolam 2 mg/kg（ M1 ） ,midazolam 4 mg/kg（ M1 ） or control（ normal saline）. Midazolam intraperitoneal injection at different dose in a volume of 10 mL/kg three times per day for 10 days. 30 min after the last injection,the mice were received a step -through passive avoidance test. The mice were killed after behavioral test ,and were divided randomly into examining LTP or levels of CaMK Ⅱ. Results Repeated administration of midazolam before the passive avoidance learning reduced step - through latencies and increased the number of errors after 24h. Administration of midazolam resulted in a dose - dependent decrease in step - through latencies and increase in the number＇s of errors . however step - through latencies and the numbers of errors were not statistically significant in group M3 and M4. Induction of LTP： we succeeded in inducting LTP in hippocampal CA1 in experimental mice . In the control group ,the spike population amplitude increased to 260.60 ± 48.62% at 60 min after high frequence stimulation as spike population amplititude before high frequence stimulation was taken as 100%. Induction of LTP in each midazolam group： In group M1 ,group M2 ,group M3 and group M4 ,the spike population amplitude increased to 208.60 ± 8.82% , 173.81 ± 10.73% , 138.41 ± 8.50% and 126.27 ± 10.52% at 60 min after high frequence stimulation,respectively. Compared to the change of spike population amplititude in group NS, there was statistically significant in group M1 , M2 , M3 and M4 , respectively. The change of spike population amplitude in group M4, M3 and M2 was significantly lower than that in group M1 after HF

关 键 词：学习 记忆 长时程增强 钙/钙调素依赖性蛋白激酶-Ⅱ 

分 类 号：R992[医药卫生—毒理学]