苯巴比妥急性干预对海马CA1区长时程增强不同阶段的影响及其机制  

The Effects of Acute Phenobarbital Application on the Different Phases of Long-term Potentiation in Rat Hippocampal CA1 Area

作　　者：吴鹏[1] 蒋莉[1] 陈恒胜[2] 

机构地区：[1]重庆医科大学附属儿童医院神经内科,重庆400014 [2]重庆医科大学附属儿童医院儿科研究所,重庆400014

出　　处：《中国细胞生物学学报》2010年第3期409-414,共6页Chinese Journal of Cell Biology

摘　　要：采用急性海马脑片,分别于长时程增强诱导前、诱导后早期及晚期进行苯巴比妥预干预、早期及晚期干预,检测其对长时程增强诱导与维持两阶段的影响及其可能机制。膜片钳技术检测发现苯巴比妥预干预可抑制长时程增强的诱导,但对双脉冲易化现象无明显影响,而早期及晚期干预未能抑制长时程增强,提示苯巴比妥可能通过突触后机制抑制长时程增强的诱导,但对维持阶段无明显影响。对长时程增强关键蛋白的Western blot检测发现,预干预组p-CaMKⅡ表达降低,而CaMKⅡ表达无变化;早期及晚期干预组CaMKⅡ及p-CaMKⅡ表达均无明显变化,提示苯巴比妥可能通过降低突触后CaMKⅡ磷酸化抑制诱导过程,其对维持阶段无抑制作用可能与对CaMKⅡ自我磷酸化及新蛋白质合成无抑制作用密切相关。To explore the effect of phenobarbital on the different phases of long-term potentiation at the therapeutic concentration in rat hippocampal CA1 area and its possible mechanisms, hippocampal slices prepared from male Wistar rats on postnatal 15 days were divided into three groups： PB pre-treatment group, PB early- treatment group and PB late-treatment group. The effects of PB on field excitatory postsynaptic potentials （fEPSPs） after high-frequency stimulation （HFS） or double-pulse stimulation were examined with patch clamp technique. The expression of calmodulin-dependent protein kinase Ⅱ （CaMK Ⅱ） and phosphorylated CaMK Ⅱ （p-CaMK Ⅱ） were examined by Western blot analysis. We found that： （1） PB inhibited fEPSPs without modifying paired-pulse facilita- tion （PPF） which solely occured presynaptically as a simple form of synaptic plasticity; （2） pretreatment with PB before HFS decreased the fEPSPs slope; （3） no significant effects of PB on fEPSPs slope were found in two maintenance phases of LTP; （4） expression of p-CaMK Ⅱ but not CaMK Ⅱ decreased in PB pre-treatment group, and however no differences were detected of p-CaMK Ⅱ and CaMK Ⅱ expression in PB early-treatment group and PB late-treatment group. The results indicated that PB inhibited the induction of LTP postsynaptically through inhibiting the expression of p-CaMK Ⅱ without modifying presynaptic neurotransmitter release and PB had no significant influence on the two maintenance phases of LTP with no effects on the expression of CaMK Ⅱ and p- CaMK Ⅱ.

关 键 词：苯巴比妥 海马脑片 认知障碍 长时程增强 双脉冲易化 

分 类 号：R96[医药卫生—药理学]