小胶质细胞p38MAPK在ATP抑制海马CA1区长时程增强中的作用  

Effect of p38 MAPK in microglia on ATP inhibition of hippocampal CA1 long-term potentiation

作　　者：宫庆娟[1,2] 陈金生[1,2] 黄乔东[1,2] 卢振和[1,2] 

机构地区：[1]广州医科大学附属第二医院疼痛科 [2]中华疼痛学会第一临床中心,510260

出　　处：《临床麻醉学杂志》2014年第2期181-184,共4页Journal of Clinical Anesthesiology

基　　金：国家自然科学基金青年基金(31100805);广州市珠江科技新星项目(2012J2200036);广东省中医药基金(20112154)

摘　　要：目的探讨p38丝裂原激活的蛋白激酶(MAPK)在三磷酸腺苷(ATP)抑制海马CA1区长时程增强(LTP)中的作用。方法成年雄性SD大鼠20只,体重250～280g,随机均分为四组:生理盐水组(NS组)、ATP组、p38 MAPK抑制剂组(SB203580组)和SB203580+ATP组。前三组在高频刺激(HFS)前30min侧脑室分别注射生理盐水、ATP和p38 MAPK;SB203580+ATP组在注射ATP前30min侧脑室给予p38MAPK抑制剂。采用海马在体电生理记录和免疫组织化学方法,记录HFS 5、60min海马CA1区兴奋性突触后电位(fEPSPs)及HFS诱导时LTP,免疫组织化学观察海马CA1区p38MAPK的磷酸化水平。结果与NS组比较,ATP组HFS 5、60min fEPSPs幅度明显降低(P<0.01)。与ATP组比较,SB203580+ATP组高频刺激后fEPSPs幅度明显增加(P<0.01),NS组、SB203580组和SB203580+ATP组海马CA1区p38MAPK的磷酸化水平明显降低(P<0.01)。p-p38仅与小胶质细胞标记物Iba-1存在共染。结论 ATP可能通过激活小胶质细胞内的p38 MAPK抑制海马CA1区LTP。Objective To explore the role of p38 mitogen-activated protein kinase （MAPK） on ATP inhibition of long-term potentiation （LTP） in hippocampal CA1 region. Methods Twenty male Sprague-Dawley rats, weighing 250-280 g, were randomly divided into four groups： intmcerebroventricular injection of normal saline, ATP and p38 MAPK was administrated 30 rain before high-frequency stimuli （HFS） in group SINS, ATP and p38MAPK （SB203580）, respectively and intracerebroventricular injection of the p38 MAPK inhibitor was administrated 30 min before ATP in group SB203580 ＋ ATP. Electrophysiological recording in hippocampus in vivo and immunohistochemistry were used. The field excitatory postsynaptic potentials （fEPSPs） and HFS-induced LTP were recorded in hippocampal CA1 region, and the phosphorylated level and location of p38 MAPK in hippocampal CA1 region were examined by using immunohistochemistry technique. Results Compare with group NS, the average amplitude of fEPSPs after HFS in group ATP was significantly decreased （P〈0. 01）. Compare with group ATP, the average amplitude of fEPSPs after HFS in group SB203580＋ATP was significantly increased （P〈0. 01）; the phosphorylation in groups NS, SB203580 and SB203580＋ ATP were significantly decreased （P〈0. 01）.Only the Iba-1 could be dyed with p-p38.Conclusion ATP might inhibit the hippocampal CA1 LTP by p38 MAPK activation in microglia.

关 键 词：长时程增强 三磷酸腺苷 P38 MAPK海马 小胶质细胞 

分 类 号：R749.16[医药卫生—神经病学与精神病学]