玻璃体内注射色素上皮源性因子对大鼠早期糖尿病视网膜病变的保护作用  

Protective effects of intravitreal injection of PEDF on early stage of diabetic retinopathy

作　　者：江新利[1] 苗慧鹏[1] 周忠友[1] 赵平[1] 刘岩[2] 

机构地区：[1]河北医科大学第三医院眼科,河北省石家庄市050051 [2]河北医科大学第三医院内分泌科,河北省石家庄市050051

出　　处：《眼科新进展》2016年第3期210-215,共6页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(编号:81100607);河北省自然科学基金资助(编号:2012206069);河北省卫生厅课题(编号:20100099;20100356)~~

摘　　要：目的观察玻璃体内注射色素上皮源性因子（pigment epithelium-derived factor,PEDF）对SD糖尿病大鼠视网膜PEDF、血管内皮生长因子（vascular endothelial growth factor,VEGF）、炎性相关因子细胞间黏附分子-1（intercellular cell adhesion molecule-1,ICAM-1）和单核细胞趋化蛋白-1（monocyte chemotactic protein-1,MCP-1）以及细胞通透性相关因子紧密连接蛋白-1（zonu-la occludens-1,ZO-1）和蛋白激酶B（protein kinase B,PKB,又称Akt）表达的影响,探讨PEDF对早期糖尿病视网膜病变的保护作用。方法选取6~8周龄SD大鼠60只,随机分为4组：正常对照组（CON组）、糖尿病组（DM组）、糖尿病生理盐水注射组（DM＋NS组）和糖尿病PEDF注射组（DM＋PEDF组）。链脲佐菌素诱导建立糖尿病模型后第1周、2周、3周时,DM＋PEDF组大鼠玻璃体内注射PEDF,而DM＋NS组注射同样体积的生理盐水。第4周时处死大鼠,摘出眼球,进行视网膜组织病理学及电镜观察。并采用免疫组织化学方法检测视网膜PEDF、VEGF、ICAM-1、MCP-1以及ZO-1、Akt的表达情况。结果糖尿病大鼠均造模成功。4周糖尿病病程尚不能导致明显的视网膜新生血管形成。在透射电镜下,DM组大鼠视网膜可见神经节细胞水肿,线粒体肿胀变大,基质肿胀明显,可见大部分或全部的嵴消失,部分双侧膜融合,粗面内质网扩张,而玻璃体内PEDF注射可以明显地改善这一病理改变。DM组大鼠PEDF主要表达于视网膜神经纤维层、神经节细胞层以及内丛状层、光感受器基质以及色素上皮层、脉络膜等部位;VEGF主要表达于神经节细胞层,ICAM-1主要表达在光感受器层,MCP-1主要表达在视网膜内层细胞,包括节细胞层和内核层,ZO-1蛋白主要表达于内核层的细胞以及神经节细胞,Akt主要表达于内丛状层以及脉络膜的细胞浆中。同CON组相比,DM组、DM＋NS组视网膜中PEDF、VEGF表达差异均无统计学意义（均为P〉0.05）Objective To observe the effects of intravitreal injection of pigment epitheliumderived factor（PEDF） on the expression of PEDF vascular endothelial growth factor（VEGF）,intercellular cell adhesion molecule-1（ICAM-1）,monocyte chemotactic protein-1（MCP-1）,zonula occludens-1（ZO-1） and protein kinase B（PKB,also Akt） in the retina of diabetic rats,and discuss the protective effects of PEDF on early stage of diabetic retinopathy.Methods 6-8 weeks old male SD rats（n =60） were randomly divided into four groups：normal control group（CON group）,diabetic group（DM group）,diabetic group with NS injection（DM ＋ NS group） and diabetic group with PEDF injection（DM ＋PEDF group）.Diabetes model was induced by intraperitoneal injection of streptozotocin（STZ）.The intravitreal injection of PEDF was performed at 1 week,2 weeks 3 weeks after the DM models was established.Eyeballs were collected after rats were sacrificed at 4 weeks of DM.The expression of PEDF,VEGF,IC AM-1,MCP-1,ZO-1 and Akt in rat retina were assessed by immunohistochemistry,and the ultrastructure of retina was studied by transmission electron microscopy.Results Diabetic rats were successfully induced.4 weeks duration of diabetes still could not result in a significant retinal neovascularization.Under transmission electron microscopy,compared with CON rats,retinal ganglion cells edema,swollen and damaged mitochondrial were all found in both DM and DM ＋ NS rats,and these pathological ultrastructural alterations could be partly ameliorated by PEDF injection.In the present study,PEDF was mainly expressed in nerve fiber layer,retinal ganglion cells,inner plexiform layer,photoreceptor matrix and retinal pigment epithelium.While VEGF was mainly expressed in retinal ganglion cell layer.ICAM-1 was found expressed in photoreceptor layer.M C P-1 was expressed in the inner retinal cells,including ganglion cells and inner nuclear layer.ZO-1 was mainly found expressed in inner nuclear layer cells and ganglion cells.Akt was expres

关 键 词：糖尿病视网膜病变 色素上皮源性因子 血管内皮生长因子 细胞间黏附分子-1 单核细胞趋化蛋白-1 紧密连接蛋白-1 蛋白激酶B 

分 类 号：R587.2[医药卫生—内分泌]