目的:探讨Fas/FasL在大鼠视网膜缺血再灌注损伤(retinal ischemia reperfusion injury,RIRI)中的表达与细胞凋亡的关系及α-硫辛酸(α-LA)的治疗作用。方法:采用升高眼内压的方法建立RIRI模型,将54只SD大鼠随机分为正常组、缺血再灌注(IR)组和α-LA干预组,IR组及α-LA干预组在12,24,48,72h光镜观察视网膜内层厚度及神经节细胞丢失,TUNEL法检测视网膜神经细胞凋亡,免疫组织化学法检测视网膜组织Fas/FasL蛋白的表达。结果:IR组视网膜内层变薄,神经节细胞数目减少。细胞凋亡出现于再灌注后12h,并逐渐递增,24h达到高峰,48h开始下降。Fas/FasL表达与凋亡的神经细胞改变基本一致。α-LA干预组视网膜内层厚度和神经节细胞数目有一定恢复。凋亡细胞在12,24,48h组明显低于IR组(P<0.05);Fas表达在12,24h组较IR组显著下降(P<0.05);FasL表达在12,24,48h组较IR组明显下降(P<0.05)。结论:Fas/FasL系统参与RIRI,导致神经节细胞凋亡;α-LA可下调Fas/FasL表达,减少神经节细胞凋亡。

AIM:To explore the relationship between the expression of Fas/FasL and the cell apoptosis in retinal ischemia reperfusion(IR)injury of rats,as well as the therapeutic effects of α-lipoic acid in the ischemic retina.METHODS:The models of retinal IR injury were made by transient elevating intraocular pressure.A total of 54 rats were divided into normal group,IR injury group and α-lipoic acid treatment group.The latter two groups were subdivided into 12,24,48 and 72 hours groups.The number of retinal ganglion cells and the thickness of the inner retinal layers were detected by HE staining method.Apoptosis was assessed by the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling method,and the expression of Fas/FasL was studied by immunohistochemistry.RESULTS:The thickness of the inner retinal layers thinned and the number of retinal ganglion cells decreased in IR injury group.There was a significant number of TUNEL positive cells 12 hours after transient ischemia followed by a decrease at the 48 hour.The expression of Fas and FasL was in coincidence with apoptosis.In treatment group,the thickness of the inner retinal layers and the number of retinal ganglion cells reduced.Apoptosis of retina and expression of Fas and FasL were obviously lower than that in IR injury group(P<0.05).CONCLUSION:α-lipoic acid can rescue retinal IR injury through downregulation of the expression of Fas/FasL.

R774.1

中国辽宁省教育厅科研基金资助项目(No.2008404)~~