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

The effect of mGluR1 expression inducing neurocyte autophagy on the learning and memory abilities in hippocampus of mouse mice with cerebral vasospasm

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 h 3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 1 （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 mGluR1 and Beclin-1 expressions. Results In Mould mould group, the learning and memory abilities were significantly lower, some neurons dis- played histopathologic changes of necrosis, the levels of mGluR1, Beclin-1 level was significantly enhanced （P 〈 0. 05 ）. Mouse treated with LY367385 had reduction in mGIuR1 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 mGluR1 in hippocampus may might induce neurocyte autophagy by activation of Beclin-1 after cerebral vasospasm.