摘要
目的：探讨尼古丁调节海马7网络振荡的机制。方法：健康雄性Wistar大鼠，取其脑组织制备海马脑片，制备好的海马脑片放入恒温（30～32℃）界面浴槽式灌流系统孵育。灌流液是充有混合气体（95％O2＋5％C02）的人工脑脊液（pH：7．35～7．50，流速2～3mL／min）。孵育1h后，采用细胞外微电极方式记录。应用红藻氨酸激动剂（Kainate）对大鼠海马脑片灌流，诱导7（20～60Hz）网络振荡。分组加入mTOR（Mammaliantargetofrapamycin）激酶阻断剂雷帕霉素，糖原合成酶激酶-3（Glycogen synthase kinase3，GSK-3）阻断剂SB415286，蛋白激酶B阻断剂Triciribine，待γ网络振荡稳定后再加入尼古丁，观察三者对尼古丁增强7网络振荡作用的影响。结果：雷帕霉素不能阻断尼古丁增强7网络振荡的效应，SB415286和Triciribine能阻断尼古丁的效应。结论：尼古丁可能通过激活糖原合成酶激酶-3（GSK-3）和蛋白激酶B（protein kinase B，Akt）来增强7网络振荡。
Objective:To investigate the mechanism of nicotinic modulation inγnetwork oscillations.Methods:The hippocampal slices had been prepared from male Wistar rats,and then had been incubated in temperature-controlled(30~32℃)interface-style bath perfusion system.The perfusion solution had been ACSF(pH:7.35~7.5with a flow rate of 2~3mL/min)filled with the mixed gas(95% O2+5% CO2).Extracellular microelectrode recording had been made after one-hour incubation.Kainic acid agonist(Kainate)had been used to induceγ(20~60Hz)oscillations.Rapamyein of the mTOR kinase antagonist,SB415286 of the GSK-3antagonist and Triciribine of the Akt antagonist had been used to observe effects of the above 3antagonists on nicotinic modulation inγnetwork oscillations.Results:Rapamyein couldn't block the enhancement ofγ oscillations induced by nicotine,but SB415286 and Triciribine could.Conclusion:GSK-3and Akt can be involved in modulation roles of nicotine inγoscillations.
