二十碳五烯酸玻璃体注射治疗糖尿病性视网膜病变的实验研究

IN VIVO RESEARCH ON TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY BY EICOSAPENTAENOIC ACID INTRAVITREOUSLY

目的探讨二十碳五烯酸(eicosapentaenoic acid,EPA)治疗糖尿病性视网膜病变(diabetic retinopathy,DR)是否有效。方法链脲佐菌素(streptozotocin,STZ)与血管内皮生长因子(vascular endothelial growth factor,VEGF)联合应用诱导产生增殖型糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)动物模型24只。随机分为D组(背景期给药组)12只、E组(增殖前期给药组)8只、F组(增殖期给药组)4只,玻璃体注射EPA,应用眼底荧光血管造影(fluorescence fundus angiography,FFA)、CD105免疫组织化学光镜观察眼底病变及阳性血管内皮细胞的变化,并与前期建立的PDR动物模型进行比较。结果 FFA结果显示,E组给药后2周内效果最佳,而D组给药后8周内均有效,随时间延长药效不断增强;E组给药后6周时效果差于D组给药后2、4、8周时;与未用药组相比,在相同的病程时均未观察到视网膜新生血管。F组给药后仍可观察到视网膜新生血管形成,并且DR也没有明显减轻。CD105免疫组织化学结果显示,相同的病程内,D组和E组未观察到CD 105阳性的视网膜血管内皮细胞,但F组仍观察到CD 105阳性血管内皮细胞。结论 EPA可以在DR背景期和增殖前期封闭VEGF受体flk-1,阻断DR的发展。

Objective To identify the utility of eicosapentaenoic acid （EPA）on diabetic retinopathy （DR）in vivo.Methods Proliferative diabetic retinopathy （PDR）Sprague-Dawley rat （n=24）was induced by application of streptozotocin associated with vascular endothelial growth factor （VEGF）.Sprague-Dawley rats were randomly divided into D group （n=1 2 ）representing medication administration group at background DR stage,E group （n = 8 ） representing medication administration group at pre-proliferation DR stage,F group （n=4 ） representing medication administration group at proliferation DR stage,then EPA was inj ected intravitreously. Fundus pathological changes were observed by fluorescence fundus angiography（FFA）,CD105 positive retinal vascular endothelial cells were observed by microscope with immunohistochemistry technique.The results were compared with diabetic rat models established in our prior study.Results FFA demonstrated the best effect in E group in two weeks after EPA＆amp;nbsp;inj ection,whereas effective and augmented time-dependently in D group during eight weeks after EPA inj ection.In six weeks after EPA inj ection in E group,the effect decreased obviously as compared with that 2,4,8 weeks after EPA injection in D group.As compared with non-medication group,retinal neovascularization was not detected at the same course of this disease. Retinal neovascularization was also detected and diabetic retinopathy was not relieved in EPA injected eyes in F group.CD105 immunohistochemistry described there were no CD105 positive vascular endothelial cells at the same course of disease in D and E group.But CD105 positive cells were still observed in F group.Conclusion EPA can suppress DR development by blocking VEGF receptor flk-1 .