小胶质细胞p38 MAPK在ATP抑制海马CA1区长时程增强中的作用

发布时间：2018-05-12 17:53

本文选题：长时程增强 + 三磷酸腺苷　；参考：《临床麻醉学杂志》2014年02期

【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(P0.01)。与ATP组比较,SB203580+ATP组高频刺激后fEPSPs幅度明显增加(P0.01),NS组、SB203580组和SB203580+ATP组海马CA1区p38MAPK的磷酸化水平明显降低(P0.01)。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。
[Abstract]:Objective to investigate the role of p38 mitogen-activated protein kinase MAPK (MAPK) in inhibiting the long-term potentiation of CA1 in hippocampus by adenosine triphosphate (ATP). Methods Twenty adult male Sprague-Dawley rats, weighing 250 ~ 280 g, were randomly divided into four groups: normal saline group (NS group), p38 MAPK inhibitor group (SB203580) and SB203580 ATP group. The first three groups were injected with normal saline ATP and p38 MAPKK SB203580 ATP before high frequency stimulation. The 30min side ventricle was treated with p38MAPK inhibitor before ATP injection. The excitatory postsynaptic potential (fEPSPs) of hippocampal CA1 and the level of p38MAPK phosphorylation in hippocampal CA1 region were observed by immunohistochemistry and electrophysiological recording of hippocampal in vivo and immunohistochemical method. The excitatory postsynaptic potential (fEPSPs) in hippocampal CA1 area and the level of p38MAPK in CA1 region of hippocampus induced by HFS were recorded by immunohistochemistry. Results compared with the NS group, the fEPSPs amplitude of the HFS group was significantly lower than that of the NS group (P 0.01). Compared with ATP group, the amplitude of fEPSPs in SB203580 ATP group increased significantly after high frequency stimulation, and the phosphorylation level of p38MAPK in CA1 region of hippocampus in SB203580 group and SB203580 ATP group decreased significantly after high frequency stimulation. It was only costained with Iba-1, a microglial marker. Conclusion ATP may inhibit LTP in CA1 area of hippocampus by activating p38 MAPK in microglia.
【作者单位】：广州医科大学附属第二医院疼痛科;中华疼痛学会第一临床中心;
【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)
【分类号】：R749.16

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