广州管圆线虫感染小鼠导致脱髓鞘性视神经炎模型的研究  

Balb/c mice infected with Angiostrongylus cantonensis: a novel animal model of demyelinatingoptic neuritis

作　　者：杨亮 牛珍 马芷璇 吴小杰 孙希 冯英[1] YANG Liang;NIU Zhen;MA Zhixuan;WU Xiaojie;SUN Xi;FENG Ying(School of Medicine,South China University of Technology,Guangzhou,Guangdong 510080,China;Department of Parasitology,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,Guangdong 510080,China;Key Laboratory of Tropical Diseases,Ministry of Education,Sun Yat-sen University,Guangzhou,Guangdong 510080,China)

机构地区：[1]华南理工大学医学院,广东广州510080 [2]中山大学中山医学院寄生虫学教研室,广东广州510080 [3]中山大学热带病防治研究教育部重点实验室,广东广州510080

出　　处：《中国热带医学》2024年第10期1225-1232,共8页China Tropical Medicine

基　　金：国家自然科学基金项目(No.82272361);广东省自然科学基金项目(No.2024A1515010615)。

摘　　要：目的构建脱髓鞘性视神经炎(demyelinating optic neuritis,DON)动物模型,为DON的研究提供参考。方法首先通过灌胃广州管圆线虫(Angiostrongylus cantonensis)幼虫的方法感染Balb/c小鼠;接着用神经行为学和视觉评分来评估小鼠神经功能学变化,视觉动作电位和视网膜电图检测小鼠视觉通路的变化,组织病理学染色和透射电镜观察小鼠视网膜和视神经髓鞘形态功能性变化,RT-qPCR和Western Blot来检测视网膜节细胞标志物Brn-3a和视神经髓鞘标志物髓鞘碱性蛋白(myelin basic protein,MBP)的变化。结果与对照组相比,Balb/c小鼠在广州管圆线虫感染后第21天,其体质量明显下降,神经行为学评分和视觉评分均显著降低;同时,视觉动作电位和视网膜电图检测结果表明视神经和视网膜的视路传导功能受损;另外,苏木素-伊红(hematoxylin-eosin,HE)染色、固蓝(luxol fast blue,LFB)染色和透射电镜观察到视网膜节细胞和视神经髓鞘出现明显损伤;最后,RT-qPCR和Western Blot结果显示视网膜神经节细胞标志物Brn-3a和髓鞘少突胶质细胞标记物MBP的蛋白水平和mRNA水平均显著降低。结论广州管圆线虫感染Balb/c小鼠可损伤其视网膜和视神经,进而导致脱髓鞘性视神经炎发生,其可作为一种新的DON动物模型。Objective Establishing an animal model of demyelinating optic neuritis(DON)to provide reference for the study of DON.Methods Balb/c mice were firstly infected with Angiostrongylus cantonensis(A.cantonensis)larvae by oral gavage.Then,neurobehavioral and visual scores were used to evaluate the neurofunctional changes in mice.Visual action potential and electroretinogram were used to detect the changes of visual pathways in mice.Histopathological staining and transmission electron microscopy were used to observe the morphological and functional changes of the retina and optic nerve myelin sheath in mice.RT-qPCR and Western Blotting were used to detect the changes of retinal ganglion cell marker Brn-3a and optic nerve myelin marker MBP.Results On the 21st day after infection with A.cantonensis,the body weight of Balb/c mice decreased significantly,and both neurobehavioral scores and visual scores were significantly reduced.At the same time,the visual action potential and electroretinogram test results showed that the visual path conduction function of the optic nerve and retina was damaged;additionally,HE staining,LFB staining,and transmission electron microscopy observed significant damage to retinal ganglion cells and optic nerve myelin;finally,RT-qPCR and Western Blotting results showed s in protein levels and mRNA levels of retinal ganglion cell marker Brn-3a and myelin oligodendrocyte marker MBP.Conclusions A.cantonensis infection in Balb/c mice can damage the retina and optic nerve,leading to demyelinating optic neuritis,which can be used as a new and ideal animal model of DON.

关 键 词：脱髓鞘性视神经炎 广州管圆线虫 BALB/C小鼠 动物模型 

分 类 号：R532[医药卫生—内科学]