奥卡西平改善NMDA诱导的视网膜病变及其机制研究

奥卡西平改善NMDA诱导的视网膜病变及其机制研究

杨欣,张勇,姚倩

西安市第四医院,十堰市太和医院,西安市第四医院

收稿日期:2018-12-31 修回日期:2019-01-22 出版日期:2019-02-25
基金资助:
湖北省卫生厅面上项目（项目编号：WJ2019M056）；十堰市科技局指导项目（项目编号：18Y32）

Protective Effects and Mechanism of Oxcarbazepine on Retinal Damage Induced by N-methyl-D-aspartate

YANG Xin,ZHANG Yong and YAO Qian

XIAN AN SHI DI SI YI YUAN,SHI YAN SHI TAI HE YI YUAN,XIAN AN SHI DI SI YI YUAN

Received:2018-12-31 Revised:2019-01-22 Online:2019-02-25

摘要/Abstract

摘要： 目的：研究奥卡西平对N-甲基-D-天冬氨酸（NMDA）诱导的大鼠视网膜病变的改善作用，并探讨其可能的作用机制。方法： 32只SD大鼠随机分为正常组、模型组、奥卡西平组、美金刚组，每组各8只。除正常组外，各组均通过双眼玻璃体内注射NMDA的方法诱导视网膜病变模型。造模后开始干预，奥卡西平组灌胃给予80 mg·kg-1奥卡西平，美金刚组灌胃给予10 mg·kg-1美金刚，正常组和模型组给予等体积生理盐水。造模后第6天，采用视网膜电图评估每组大鼠视功能的差异。视网膜行苏木精-伊红（HE）染色以及Brn3免疫荧光染色观察其形态学和视网膜神经节细胞数的变化。采用蛋白免疫印迹法检测大鼠视网膜中Cleaved caspase-3、Caspase-3、 Bax、Bcl-2等蛋白的表达变化。结果：与模型组相比较，奥卡西平组及美金刚组大鼠明视负向反应（PhNR）振幅增加（P＜0.05），视网膜厚度增加以及视网膜神经节细胞的数目增加（P＜0.05），视网膜中的Cleaved caspase-3/Caspase-3、 Bax/Bcl-2的蛋白表达水平比值降低（P＜0.05）。结论：奥卡西平能通过抑制凋亡通路改善NMDA诱导的视网膜病变。

Abstract: Objective： To investigate the protective effect and mechanism of oxcarbazepine on rat retinal damage induced by N-methyl-D-aspartate（NMDA）. Methods： 32 SD rats were randomly divided into the normal group， model group， memantine group and oxcarbazepine groups， 8 rats in each group. Retinal damage was induced by injecting NMDA intravitreally except for the normal group. The rats were treated with 80 mg·kg-1 oxcarbazepine (by gavage) in oxcarbazepine group. Memantine group rats were treated with 10 mg·kg-1 memantine by gavage. The normal group and the model group were treated with saline at equivalent volume. On 6th Day， electroretinogram (ERG) was employed to evaluate changes in visual function. HE staining and Brn3 immunofluorescent staining were used to evaluate the changes of retinal histology and retinal ganglion cells (RGCs) numbers in different groups. Expression level of apoptosis related proteins Cleaved caspase-3， Caspase-3， Bax and Bcl-2 were analyzed by western blot. Results： Compared with model group， the amplitudes of PhNR in memantine group and oxcarbazepine group significantly increased(P＜0.05)， meanwhile increasing the rat retina thickness and the cell number in ganglion cell layer (GCL) were increased(P＜0.05). In addition， the ratio of Cleaved caspase-3/Caspase-3 and Bax/Bcl-2 were effectively decreased(P＜0.05). Conclusion： Oxcarbazepine can effectively improve the pathological process of retinal damage induced by NMDA， and the mechanism may be related to the inhibition of apoptotic pathway.

杨欣,张勇,姚倩. 奥卡西平改善NMDA诱导的视网膜病变及其机制研究[J]. .

YANG Xin,ZHANG Yong and YAO Qian. Protective Effects and Mechanism of Oxcarbazepine on Retinal Damage Induced by N-methyl-D-aspartate[J]. .

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