活化的巨噬细胞在外伤性视神经损伤修复中的作用

发布时间：2018-04-30 14:12

本文选题：视神经损伤 + 动物模型　；参考：《天津医科大学》2012年硕士论文

【摘要】：目的：(1)通过建立中国白兔外伤性视神经损伤动物模型,观察并比较视神经损伤后是否联合晶状体损伤时视网膜、视神经单核/巨噬细胞浸润与视网膜神经节细胞轴突再生的关系,探讨单核/巨噬细胞在视神经损伤修复中的作用。(2)应用SPIO作为对比剂进行视网膜、视神经磁共振成像,对视神经损伤联合晶状体损伤后单核/巨噬细胞在组织内的迁徙、存活情况进行动态观察,为临床提供一种通过动态观察单核/巨噬细胞的变化规律监测视神经损伤修复过程的新方法。方法：成年中国白兔共64只,体重2～2.5kg,选取右眼作为实验组,左眼作为对照组,每组各64眼。实验组(视神经联合晶状体损伤组)：应用液压冲击颅脑损伤仪(Fluid Percussion Brain Injury Device, FPI)建立外伤性视神经损伤动物模型,同时用半寸针灸针从眼球赤道部垂直刺入巩膜5～6mm,损伤晶状体赤道部,建立视神经联合晶状体损伤模型。对照组(单纯视神经损伤组)：应用FPI建立单纯外伤性视神经损伤动物模型。每组按照损伤后1、2、4、7、10、14、21、28天等观察时间点随机分为8个亚组,每亚组8只。分别在各观察时间点之前24h,经兔耳缘静脉注射SPIO (Resovist; Schering, Berlin, Germany),0.2mmol/kg。分别于损伤前及损伤后各观察时间点行双眼闪光视觉诱发电位(Flash-Visual Evoked Potential, F-VEP)及视神经磁共振成像(Magnetic Resonance Imaging, MRI)检测；检测后摘取双眼眼球行视网膜、视神经组织病理学特殊染色及免疫组化检测。结果：(1)F-VEP:实验组损伤后10天内潜伏期逐渐延长(P0.05),10天后潜伏期逐渐缩短(P0.05)；振幅在损伤后7天内逐渐降低(P0.05),7天后逐渐升高(P0.05)。对照组损伤后14天内潜伏期逐渐延长(P0.05),14天后有缩短趋势(P0.05)；振幅在伤后10天内逐渐降低(P0.05),10天后有反弹的趋势,但是这种反弹趋势无统计学意义(P0.05)。伤后28天实验组与对照组的振幅差异有统计学意义(P0.05)。(2)视神经MRI：损伤前中国白兔视神经清晰可见呈中等信号,眶内结构规整。损伤后1天右眼晶状体形状不规整,双眼视神经距眼球2.0～4.5mm处信号增高,眶内结构紊乱；损伤后10天中国白兔右眼视神经周围可见大量低信号,而左眼仍以高信号为主,双眼视神经周围结构紊乱；损伤后28天中国白兔双眼眼视神经周围信号不均,左眼视神经周围仍可见少量高信号。(3)视网膜病理：实验组损伤后4天视网膜、视神经开始出现活化的单核/巨噬细胞,之后逐渐增多,到10天达到最高峰,10天以后活化的单核/巨噬细胞数量逐渐减少,28天后消失；而对照组各亚组损伤后不同时间点均未监测到活化的单核/巨噬细胞。实验组损伤后4天视网膜开始出现轴突再生的视网膜神经节细胞,之后逐渐增多,而对照组各亚组损伤后不同时间点均未监测到轴突再生的视网膜神经节细胞。结论：(1)视神经损伤后,活化的单核/巨噬细胞能够促进RGCs存活和轴突再生,在视神经损伤修复中起着重要作用；(2)应用SPIO作为对比剂进行视网膜、视神经磁共振成像能够很好地对单核/巨噬细胞在组织内的迁徙、存活情况进行动态观察,可用于检测视神经损伤修复。
[Abstract]:Objective : ( 1 ) To observe and compare the relationship between retinal and optic nerve mononuclear / macrophage infiltration and retinal ganglion cell axon regeneration after optic nerve injury by establishing the animal model of traumatic optic nerve injury in Chinese white rabbits .

Methods : Sixty adult Chinese rabbits were randomly divided into 8 subgroups according to 1 , 2 , 4 , 7 , 10 , 14 , 21 , 28 days after injury .
After detection , the retina and optic nerve tissue pathology were examined by special staining and immunohistochemistry .

Results : ( 1 ) F - VEP : The latency of F - VEP was gradually prolonged within 10 days after injury ( P0.05 ) .
The amplitude of the control group gradually decreased within 7 days after injury ( P0.05 ) , and gradually increased after 7 days ( P0.05 ) .
There was no significant difference in amplitude between the experimental group and the control group ( P0.05 ) .
There were a lot of low signals around the optic nerve of the right eye of Chinese white rabbits 10 days after injury , while the left eye was still dominated by high signal , and the optic nerve of both eyes was disordered around the optic nerve ;
There was a small number of high signals around the optic nerves around the optic nerve of the eyes of Chinese white rabbits 28 days after injury . ( 3 ) retina pathology : the retina and optic nerve began to appear activated monocytes / macrophages in 4 days after injury , then gradually increased , reached the highest peak in 10 days , the number of activated monocytes / macrophages decreased gradually after 10 days , and disappeared after 28 days ;
In the control group , the activated monocytes / macrophages were not detected at different time points after injury . The retinal ganglion cells with axonal regeneration began to appear in the retina at 4 days after the injury , and the retinal ganglion cells were not detected at different time points after injury in the control group .

Conclusion : ( 1 ) After optic nerve injury , activated monocytes / macrophages can promote the survival and axonal regeneration of RGCs and play an important role in the repair of optic nerve injury ;
( 2 ) Using SPIO as the contrast agent to carry on the retina , the optic nerve magnetic resonance imaging can well observe the migration and survival of the mononuclear / macrophage in the tissue , and can be used for detecting optic nerve injury repair .

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R779.1

【参考文献】