Fas/FasL系统在大鼠视网膜缺血再灌注凋亡损伤中的作用及bFGF的影响(英文)  

Expression of Fas/FasL ligand and cell apoptosis in ischemia/reperfusion-induced retina and effects of bFGF

作　　者：赵颖[1] 牛膺筠[1] 周占宇[1] 高云霞[1] 王红云[1] 

机构地区：[1]青岛大学医学院附属医院眼科,中国山东省青岛市266003

出　　处：《国际眼科杂志》2005年第3期423-427,共5页International Eye Science

基　　金：中国山东省教委基金资助(No.J00K53)~~

摘　　要：目的:探讨Fas/FasL在大鼠视网膜缺血再灌注损伤中的表达与细胞凋亡的关系及碱性成纤维细胞生长因子(basicfibroblastgrowthfactor,bFGF)的影响。方法:前房加压法制作大鼠视网膜缺血再灌注损伤模型,28只大鼠随机分为正常组和手术组,其中手术组大鼠左眼为缺血再灌注组,右眼为治疗组,手术组又按照再灌注后不同时间段分为1,6,12,24,48,72h组。应用末端脱氧核酸转移酶介导的脱氧三磷酸尿苷缺口末端标记法检测视网膜神经细胞凋亡指数(apoptosisindex,AI),免疫组织化学法检测视网膜组织中Fas,FasL的表达。结果:视网膜神经细胞的凋亡出现于再灌注后6h,并逐渐递增,24h达到高峰,48h开始下降,72h组不明显。Fas,FasL表达改变与凋亡的神经细胞改变基本一致。bFGF治疗组各观察指标表达变化规律与缺血组基本一致,但AI值在12,24,48h组明显低于缺血组(P<0.05);Fas表达在6,12,24h组较缺血组显著下降(P<0.05);FasL表达在12,24,48h组较缺血组明显下降(P<0.05)。结论:Fas/FasL死亡诱导系统参与视网膜缺血再灌注损伤,导致神经节细胞的凋亡;bFGF可抑制Fas、FasL的表达,减少神经节细胞凋亡,对视网膜缺血再灌注损伤有治疗作用。· AIM: To explore the relationship between the expression of Fas/FasL and the apoptosis in retinal ischemia/reperfusion injury of rats, as well as the therapeutic effects of basic fibroblast growth factor(bFGF)on the ischemic retina.· METHODS: The models of retinal ischemia/reperfusion injury were made by transiently elevating introcular pressure. A total of 28 rats were divided into Normal Group and Operative Group. The latter were subdivided into 1, 6, 12, 24, 48 and 72h after reperfusion, in which the left eyes of the rats were in the ischemia/reperfusion groups and the right ones were in the treatment groups(bFGF intracameral injection). Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) method, and the expression of Fas/FasL ligand was studied by strept avidin-biotin complex (SABC)immunohistochemistry. · RESULTS: No positive cells were observed in the normal rats' retinae, but there were a significant number of TUNEL positive cells in 6-24h after transient ischemia followed by a decrease at 48h. The number of TUNEL positive cells reached a maximum at 24h after ischemia. The expression of Fas gradually increased as early as at 6h, reached a peak at 24h, then decreased at 48h. Similarly, the expression of Fas ligand was at peak in 24 -48h in GCL and INL of retina. bFGF ministered before reperfusion inhibited apoptotsis and ameliorated the tissue damage. It also diminished Fas and FasL expression in ischemic/reperfused retina. · CONCLUSION: Retinal ischemia-reperfusion after transiently elevated IOP induced apoptosis of cells in the retina. Fas/FasL may have an important role in the early events of the apoptotic pathways. bFGF can rescue RGCs from retinal ischemia/reperfusion injury through down-regulation of Fas and Fas ligand expression and may represent an important mechanism for therapeutic neuroprotection. ·

关 键 词：FAS/FASL系统 大鼠 视网膜 缺血再灌注 细胞凋亡 细胞损伤 BFGF 基因表达 

分 类 号：R774.1[医药卫生—眼科]