蛛网膜下腔出血后自噬活性调节中代谢型谷氨酸受体1与细胞外信号调节激酶的作用及其相互关系  

Roles and relationship between mGluR1 and ERK in regulating the autophagic activity after subarachnoid hemorrhage

作　　者：李冉[1] 刘江[1] 崔建忠 阚泉[1] 王凯杰 张宇新[1] 高俊玲[1] 

机构地区：[1]河北联合大学基础医学院 [2]工人医院神经外科,唐山063000

出　　处：《解剖学杂志》2012年第6期713-717,共5页Chinese Journal of Anatomy

基　　金：河北省自然科学基金（H2012401071）;河北省卫生厅医学科学研究重点计划指令项目（20110164）

摘　　要：目的：探讨蛛网膜下腔出血（SAH）后代谢型谷氨酸受体1（mGluR1）与细胞外信号调节激酶1／2（ERK1／2）对神经细胞自噬的影响。方法：采用非开颅血管内穿线法制备小鼠SAH模型，随机分为对照组、模型组、mGluR1拮抗剂LY367385组，分别在SAH术后6、24、48h3个时相点取脑组织标本，H-E染色观察右侧海马CA1区组织学变化，并计算存活神经元数目，逆转录-聚合酶链式反应检测各组mGluR1 mRNA表达变化，免疫印迹检测mGluR1、磷酸化ERK1／2（p-ERK1／2）、beclin-1蛋白表达。结果：与对照组比较，模型组小鼠神经功能评分显著降低，海马CA1区部分神经细胞变性坏死，存活神经元数目减少，随SAH时间延长，各组小鼠mGluR1mRNA、mGluR1、p-ERK1／2、beclin-1蛋白均有不同程度增强。与模型组比较，拮抗剂组小鼠存活神经元数目增加，mGluR1mRNA、mGluR1、p-ERK1／2和beclin-1蛋白表达均有不同程度下调，并且神经功能评分得到改善。结论：SAH后mGluRl表达增强可通过激活ERK1／2信号途径诱导大脑海马区神经细胞自噬。Objective：To investigate the role of metabotropic glutamate receptor 1 （mGluR1） and extracelluIar signal regula- ted kinase （ERK） in regulating the neurocyte autophagic activity after subarachnoid hemorrhage （SAH）. Methods： Male ICR mice were randomly divided into three groups： a sham operation group, a model group and LY367385 group. Ten minutes after SAH, 5 μ1 LY367385 or NS were microinjected into the lateral cerebral ventricle. In SAH model by endovascular perforation without opening cranium, the score of neuroethology was measured after SAH and treatment. At different time points （6, 24, 48 h） after operation, the cerebral tissues were sampled, the histopathologic changes of hippocampus CA1 area were observed by HE staining method, and the number of survival/apoptotic neurons was counted separately. Western blotting assay was used to examine p-ERK1/2 and beclin- 1 expression, and the expression of mGluR1 mRNA was detected using RT-PCR. Results： In the model group, the neuroethology score was significantly lower. Some neurons displayed histopathologic changes of necrosis. The survival neurons were much less than those in the sham group. The mGluR1 rnRNA, mGluR1, p-ERK1/2 and beclin-1 level was significantly enhanced. The mice treated with LY367385 had a reduction in mGluR1 mRNA, mGluR1, ERK1/2 activity and beclin-1 level. The sur- vival neurons were higher, and the neurological score was relieved in LY367385 group. Conclusion： The increased expres- sion of mGluR1 in the hippocampus may induce neurocyte autophagy by activation of ERK1/2 signaling pathway after SAH.

关 键 词：蛛网膜下腔出血 代谢型谷氨酸受体 细胞外信号调节激酶 自噬 

分 类 号：R575.2[医药卫生—消化系统]