摘要
目的本研究拟建立大鼠急性视神经钳夹伤模型,确立视神经受损后视网膜组织中不同时间神经调节蛋白1（neureg-ulin-1,NRG-1）表达的情况,研究NRG-1是否对视神经急性损伤有保护和修复作用。方法 2月龄SD雄性大鼠48只随机分为对照组（即假手术组,24只）和实验组（24只）;钳夹伤后2h、1d、2d、7d、2周、4周各组行闪光视觉诱发电位（flash visual evokedpotential,FVEP）检查及眼底照相观察视神经受损情况,并于钳夹伤后每个时间点处死动物各4只,摘除眼球和视神经,用组织病理检查和免疫组织化学等技术来观察和评价视网膜组织内NRG-1表达水平。结果急性视神经钳夹伤后2h、1d、2d、7d大鼠眼底像与正常眼相比尚无明显差别,至2周时视盘逐渐变淡白,4周时苍白程度基本定型。FVEP：实验组大鼠夹伤后2h即出现异常波形,呈低平扁阔及不规则形,潜伏期延长,P100波波幅降低;随后稍有恢复,但仍低于正常振幅的50%。P100波振幅及其潜伏期在损伤后各时间点与假手术组比较,差异均有统计学意义（均为P〈0.05）。HE染色：假手术组大鼠视网膜轻度水肿、增厚,胞核数量及排列无明显改变;实验组夹伤后2h视网膜组织水肿,其中神经纤维层与内网状层的水肿最明显,厚度增加明显,染色较淡;夹伤后1~2d视网膜神经节细胞减少,细胞变性,神经纤维层明显变薄,内核层细胞排列紊乱,外核层变薄;夹伤后7d、2周、4周时变化不明显。NRG-1表达情况：实验组大鼠急性视神经损伤后2h、1d、2d、7d、2周视网膜的NRG-1蛋白阳性细胞表达分别为（25.36±1.36）mm-2、（39.78±3.78）mm-2、（65.13±8.13）mm-2、（87.26±10.36）mm-2、（137.62±14.08）mm-2,假手术组分别为（16.57±1.46）mm-2、（21.32±2.04）mm-2、（14.33±4.14）mm-2、（16.02±3.04）mm-2、（18.03±3.72）mm-2,实验组均明显高于假手术组大鼠（均为P〈0.05）;其中,损伤后2周时NRG-1的表达量升高最为明显,达到峰值;此后逐渐下降。至损伤后4周,实验组与假手术组大鼠视网膜组织相比,NRG-1的表达差异无统计学意义（P〉0.05）。结论大鼠急性视神经损伤后NRG-1蛋白的表达先升高后降低,NRG-1对于正常大鼠视功能的维持有着一定作用,NRG-1可能参与了视神经损伤的病理变化和自身修复过程。
Objective To set up the model of acute optic nerve ring clamp injury,determine the expression of neuregulin-1（NRG-1）in retinal tissues at different time points after injury,and investigate whether the NRG-1 has the protective and prothetic effect on acute optic nerve injury.Methods Forty-eight male SD rats with 2 months old were randomly divided into control group（sham operation group）and experimental group,24 cases in each group,the optic nerve injury in each group was qualitatively observed by flash visual evoked potential and fundus photograph at 2 hours,1 day,2 days,7 days,2 weeks and 4 weeks after ring clamp injury,4 cases were sacrificed at each time point,the eyeballs and optic nerve were selected,the expression of NRG-1 in retinal tissue was determined by histopathology and immunohistochemistry.Results The fundus photography at 2 hours,1 day,2 days and 7 day after acute optic nerve injury showed that the optic disc gradually became pale at 2 weeks and the degree of pale was stable at 4 weeks.The flash visual evoked potential showed that the abnormal wave appeared in the experimental group at 2 hours after injury,the wave was in low,thin and flat with irregular shape,the latency was long,the amplitude of P100 wave was decreased and then recovered,but still lower than the half of normal.Compared with the control group,there were statistical differences in amplitude and latency of P100 wave in the experimental group at different time points after injury（all P0.05）.The HE staining results showed that the retina of control group was slightly edematus and thick,the number and arrangement of cell nucleus had no obvious change;In the experimental group,the retinal tissue was edematus at 2 hours after injury,especially the nerve fiber layer and inner plexiform layer with obviously increased thickness and slightly staining,the retinal ganglion cells were decrease and degenerative,the inner nuclear layer cells were irregular,and the outer nuclear layer was thin,which had no obviously change at 4 weeks.The expression of NRG-1 protein in retina of the experimental group at 2 hours,1 day,2 days,7 days and 2 weeks after acute injury were（25.36±1.36）mm-2,（39.78±3.78）mm-2,（65.13±8.13）mm-2,（87.26±10.36）mm-2 and（137.62±14.08）mm-2,respectively,which in retina of the control group were（16.57±1.46）mm-2,（21.32±2.04）mm-2,（14.33±4.14）mm-2,（16.02±3.04）mm-2 and（18.03±3.72）mm-2,respectively,there were statistical differences between two groups（all P0.05）.The expression of NRG-1 peaked at 2 weeks after injury,then gradually decreased,at 4 weeks after injury there was no statistical difference between two group（P0.05）.Conclusions The expression of NRG-1 protein is increase and then decrease after injury.NRG-1 plays an certain role in maintaining the normal retinal function,and may be taken part in the pathologic changes and self-repair procession of injured optic nerve.
出处
《眼科新进展》
CAS
北大核心
2010年第11期1021-1025,共5页
Recent Advances in Ophthalmology
