睫状神经营养因子联合复光颗粒对外伤性视神经损伤修复作用的实验研究

发布时间：2018-04-27 09:32

本文选题：TON + CNTF　；参考：《吉林大学》2013年博士论文

【摘要】：本文通过实验研究睫状神经营养因子（ciliary neurotrophic factor，CNTF）联合中药复光颗粒对白兔外伤性视神经病变（traumatic optic neuropathy，TON）治疗的病理形态学、超微结构、视觉电生理及生物力学特性的影响，探讨睫状神经营养因子和复光颗粒对TON可能的保护机制，为临床治疗TON提供一定的理论依据。首先建立了轻、中、重不同程度的钳夹伤白兔视神经损伤模型，观察不同程度损伤后不同时间视神经视网膜组织学的变化，结果表明应用蚊式血管钳可制作白兔不同程度的视神经钳夹损伤模型，模型重复性好，致伤程度稳定，可用于临床研究。轻度损伤组视网膜及视神经损伤后病理形态改变不显著，视网膜神经节细胞（retinal ganglioncell，RGC）数量变化不明显，视神经结构和功能可大部分自行修复。中度损伤组视网膜及视神经病理形态改变明显，损伤时间越长，病理变化越明显。重度损伤组视网膜及视神经病理形态不可逆性改变，正常结构几乎完全消失，视网膜及视神经功能丧失。证明白兔中度损伤视神经模型可以作为TON发病机制及药物治疗效果研究的良好的动物模型。在确定致伤程度稳定、重复性好的白兔TON中度钳夹伤模型后，建立正常对照组、损伤组、CNTF治疗组、复光颗粒治疗组、CNTF和复光颗粒联合治疗组。通过实验观察中度视神经钳夹伤白兔模型的病理形态学、超微结构、视觉电生理学及生物力学特性的变化，得出以下结论：视神经损伤后病理形态学改变包括RGC和神经纤维数目不断减少，出现RGC肿胀，核固缩、染色加深，染色质边聚、空化、变性，细胞核碎裂等细胞凋亡现象。视神经纤维水肿，胶质细胞肿胀，神经纤维断裂、结构模糊，坏死灶增多、扩大，各层神经组织明显变薄、萎缩。视神经损伤超微结构改变主要包括视神经和视网膜的神经纤维层线粒体肿胀、嵴变宽甚至空泡化，微丝和微管数目减少、结构异常，轴突数目减少，RGC细胞凋亡等结构的改变，损伤随时间的延长逐渐加重。视神经损伤后闪光刺激诱发电位变化包括P1波潜伏期延长，振幅降低，传导能力减弱。损伤后视神经生物力学改变包括抗拉伸承载能力减弱，拉伸最大载荷、最大应力、最大应变、弹性限度载荷、弹性限度应变、弹性限度应力明显小于正常神经。CNTF和复光颗粒能够在一定程度上减缓RGC和神经纤维的凋亡时间和数量，促进RGC和神经纤维的再生，阻止轴突的变性坏死，从而阻断RGC的死亡，保护视神经超微结构，为轴浆运输功能的恢复提供物质基础和载体，促进神经纤维再生，缩短视神经P1波的潜伏期，增加振幅，增强传导能力，增强视神经抗拉伸承载能力，促进视神经的修复，CNTF和复光颗粒联合应用效果更佳。本文的创新点如下： 1、从病理形态学、超微结构、视觉电生理学及生物力学多角度观察兔视神经损伤模型的视神经及视网膜的改变。 2、建立了不同程度的钳夹伤兔视神经损伤模型，根据病理形态学变化筛选出可作为TON发病机制及药物治疗效果研究的有效动物模型。 3、采用纵向拉伸实验，分别获取正常对照组、损伤组、CNTF治疗组、复光颗粒治疗组、CNTF和复光颗粒联合治疗组兔视神经的最大载荷、最大应力、最大应变、弹性限度载荷、弹性限度应变、弹性限度应力等，利用回归分析方法建立视神经应力-应变关系表达式，绘制应力-应变曲线，并进行定量分析。 4、从病理形态学、超微结构、视觉电生理学及生物力学角度分别观察CNTF、复光颗粒以及CNTF和复光颗粒联合对兔视神经损伤的修复程度，结果证明CNTF和复光颗粒联合治疗效果更佳。
[Abstract]:In this paper , the effects of ciliary neurotrophic factor ( CNTF ) combined with Chinese traditional Chinese medicine ( CNTF ) on the pathomorphology , ultrastructure , visual electrophysiology and biomechanical properties of traumatic optic neuropathy ( TON ) in rabbits were studied .

The optic nerve injury model of rabbits with different degrees of injury was established , and the changes of optic nerve retinal histology were observed . The results showed that the pathological changes of retina and optic nerve were not significant after injury . The changes of optic nerve structure and function were not significant . The changes of optic nerve structure and function were not significant .

The changes of pathological morphology , ultrastructure , visual electrophysiology and biomechanical properties of rabbits with moderate optic nerve injury were observed . It can promote nerve fiber regeneration , shorten the latency of optic nerve P1 wave , increase amplitude , enhance conduction ability , strengthen optic nerve anti - tension bearing capacity , promote optic nerve repair , CNTF and complex light particle combined application effect better .

The innovation points of this paper are as follows :

1 . The changes of optic nerve and retina in rabbit optic nerve injury model were observed from pathological morphology , ultrastructure , visual electrophysiology and biomechanical multi - angle .

2 . The model of optic nerve injury of rabbits with different degrees of jaw injury was established , and an effective animal model which can be used as the mechanism of TON pathogenesis and the effect of drug therapy was screened according to the pathomorphological changes .

3 . The maximal load , the maximum stress , the maximum strain , the elastic limit load , the elastic limit strain and the elastic limit stress were obtained from the normal control group , the injured group , the CNTF treatment group , the complex light particle treatment group , the CNTF and the complex light particle combination treatment group , and the stress - strain curve was drawn and the quantitative analysis was performed .

4 . The degree of repair of optic nerve injury in rabbits was observed from pathomorphology , ultrastructure , visual electrophysiology and biomechanical angle , and the results showed that CNTF combined with complex light particles had better effect on treatment of optic nerve injury in rabbits .

【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R774.6

【参考文献】