重力打击式小鼠外伤性视神经病变模型的建立及外伤性视神经病变发病机制的探讨  

Establishment of the gravity strike model of mouse traumatic optic neuropathy and analysis on its mechanisms

作　　者：陈彦婷[1] 林晓峰[2] CHEN Yanting;LIN Xiaofeng(Hainan Eye Hospital and Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,Haikou 570311,Hainan Province,China;State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,Guangzhou 510060,Guangdong Province,China)

机构地区：[1]中山大学中山眼科中心海南眼科医院(海南省眼科医院),海南省眼科学重点实验室,海南省海口市570311 [2]中山大学中山眼科中心眼科学国家重点实验室,广东省广州市510060

出　　处：《眼科新进展》2021年第9期821-825,共5页Recent Advances in Ophthalmology

基　　金：国家自然科学基金面上项目(编号81570861)。

摘　　要：目的通过建立重力打击式小鼠外伤性视神经病变模型探讨外伤性视神经病变的发病机制。方法选取SPF级C57BL/6J成熟小鼠48只(96眼),均取小鼠左眼为实验眼进行造模,右眼为对照眼不做处理。采用重力打击建立小鼠外伤性视神经病变模型,造模后第1、3、5、7天对小鼠进行观察,每个时间点取6只小鼠进行闪光视觉诱发电位检查、视网膜组织HE染色,另取6只小鼠利用RT-PCR检测小鼠实验眼和对照眼视网膜中白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-αmRNA的表达情况。结果闪光视觉诱发电位检查结果显示,对照眼和实验眼均能检测出明显的负向波形,本实验命名为N1波。在造模后第1、3、5、7天,小鼠实验眼闪光视觉诱发电位振幅均显著低于对照眼,差异均有统计学意义(均为P<0.001)。造模后,对照眼的视网膜结构层次清晰,视网膜神经节细胞排列整齐,胞核清楚,核膜光滑完整;实验眼造模后视网膜轻度增厚,视网膜神经节细胞层可见细胞间空泡形成,视网膜神经节细胞排列出现紊乱,在造模后第7天可见神经节细胞核出现缺失。造模后第1、3、5、7天小鼠实验眼视网膜中IL-1βmRNA和TNF-αmRNA相对表达量均明显低于对照眼(均为P<0.05);对照眼和实验眼视网膜中IL-1βmRNA和TNF-αmRNA相对表达量均随时间进展呈下降趋势(均为P<0.05)。结论本研究建立的重力打击式小鼠外伤性视神经病变模型操作简便,模拟临床效果更好,外伤性视神经病变小鼠视网膜IL-1β、TNF-α呈现高表达。Objective To investigate the pathogenesis of traumatic optic neuropathy by establishing a gravity strike model of traumatic optic neuropathy in mice.Methods A total of 48 mature C57BL/6J mice(96 eyes)in specific pathogen free(SPF)level were selected.Their left and right eyes were considered as the experimental and control groups,respectively.The traumatic optic neuropathy model of mice was established by a gravity strike on the left eye.Mice were observed on the 1st,3rd,5th and 7th day after modeling.At each time point,6 mice were taken for flash visual evoked potential(F-VEP)examination and HE staining of retinal tissues.Expression levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the experimental and control retina were detected by RT-PCR.Results F-VEP results showed that a significant negative wave was detected in both the control eye and the experimental eye,which was named as N1 wave in this experiment.On day 1,3,5 and 7 of the experiment,the amplitude of F-VEP in experimental eyes was significantly lower than that in control eyes(all P<0.001).After modeling,the retinal of the control eye had a clear structure,well orderly arranged retinal ganglion cells,and clear nuclei with smooth and complete nuclear membrane.On the contrary,slightly thickened retina,the formation of intercellular vacuoles and disordered arrangement of ganglion cells in the retinal ganglion cell layer,and the loss of ganglion nuclei was observed on the 7th day of experimental eye.Expression levels of IL-1βand TNF-αin the experimental retina of was significantly lower than that of controls at the 1st,3rd,5th and 7th day after modeling(all P<0.05),which were downregulated with the prolongation of modeling(all P<0.05).Conclusion The gravity strike model of traumatic optic neuropathy in mice established in this study is simple to operate and has a better clinical simulation effect.In this model,IL-1βand TNF-αwere upregulated in the retina of mice with traumatic optic neuropathy.

关 键 词：外伤性视神经病变 闪光视觉诱发电位 白细胞介素-1Β 肿瘤坏死因子-Α 小鼠 动物模型 

分 类 号：R774[医药卫生—眼科]