mGluR1蛋白诱导海马组织自噬对脑血管痉挛小鼠学习记忆能力的影响

摘要

目的 探讨小鼠脑血管痉挛(CVS)后代谢型谷氨酸受体1(mGluR1)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CVS模型,随机分为假手术组、模型组、mGluR1拮抗剂LY367385组,于术后10 min侧脑室注射生理盐水或LY367385(500 nmol)5μl,采用Y型电迷宫检测小鼠自主活动及学习记忆能力.分别于SAH术后6、24、48 h3个时相点取脑组织标本,HE染色观察右侧海马CA1区组织学变化,免疫印迹法检测mGluR1、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,随痉挛时间延长,各组小鼠mGluR1、Beclin-1蛋白均有不同程度增强(P＜0.05).与模型组比较,拮抗剂组mGluR1、Beclin-1蛋白表达均有不同程度下调(P＜0.05),并且神经功能评分得到改善.结论 脑血管痉挛后mGluR1表达增强可通过激活Beclin-1途径诱导小鼠海马区神经细胞自噬.%Objective To investigate the role of metabotropic glutamate receptors l(mGluRsl) in regulating the neurocyte autoph-agic activity after cerebral vasospasm ( CVS). Methods Male ICR mouse were randomly divided into three groups; sham operation group, Model model group and LY367385 groups, 10 minutes after subarachnoid hemorrhage(SAH) , 5 ul μl of LY367385 or NS were microinjected into lateral cerebral ventricle respectively. SAH model by endovascular perforation without opening cranium, the Y-maze's rational were used to test the learning and memory abilities. At different time points(6, 24, 48 h)after operation, the tissues of cerebral were sampled, the his-topathologic changes of hippocampus CA1 area were observed by HE staining method, and Western blot assay was used to examine mGluRl and Beclin-1 expressions. Results In Mould mould group, the learning and memory abilities were significantly lower, some neurons displayed histopathologic changes of necrosis, the levels of mGluRl, Beclin-1 level was significantly enhanced(P <0. 05). Mouse treated with LY367385 had reduction in mGluRl activity and Beclin-1 level (P <0. 05) , the living neurons were higher, and the learning and memory a-bilities were relieved of LY367385 group. Conclusions The increased expression of mGluRl in hippocampus may might induce neurocyte autophagy by activation of Beclin-1 after cerebral vasospasm.