过氧化物酶体增生物激活受体-γ激动剂对糖尿病大鼠视网膜核因子-κB表达和视网膜神经节细胞凋亡的影响  

Effect of peroxisome proliferator-activated receptor-gamma excitomotor on the expression of nuclear factor- kappa B and apoptosis of retinal ganglion cells in rat retina with diabetes mellitus

作　　者：苟文军[1] 欧阳科[1] 吕红彬[1] 李青兰[1] 周琦[1] 张俊[1] 

机构地区：[1]泸州医学院附属医院眼科,646000

出　　处：《中华实验眼科杂志》2012年第8期709-714,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：四川省教育厅基金项目（08ZA092）

摘　　要：背景糖尿病视网膜病变（DR）作为糖尿病最常见的眼部微血管并发症，已成为人类最重要的致盲性眼病之一。核因子-κB（NF-κB）可通过激活一系列的炎性因子，参与DR的发生与发展。目的观察过氧化物酶体增生物激活受体-γ（PPAR-γ）激动剂罗格列酮对链脲佐菌素（STZ）诱导的早期糖尿病大鼠视网膜中NF-κB的表达及其对视网膜神经节细胞（RGCs）凋亡的影响。方法选择90只健康雄性SPF级Wistar大鼠，应用随机数字表法随机将大鼠分为3个组：正常对照组、糖尿病对照组和罗格列酮治疗组，其中糖尿病对照组和罗格列酮治疗组均采用一次性腹腔注射50mg／kgSTZ的方法建立糖尿病大鼠模型。自糖尿病模型成模后第3天起，罗格列酮治疗组大鼠每日给予罗格列酮3mg／kg灌胃，正常对照组和糖尿病对照组每日给予等体积的生理盐水灌胃。3个组分别于给药后4、8、12周各取10只大鼠处死，处死前检测各组大鼠的血糖，然后摘除眼球制作眼杯标本，并进行常规组织病理学检查，采用免疫组织化学法检测视网膜中NF-κBp65蛋白的表达，采用TUNEL法测定RGCs的凋亡指数（AI）。结果给药后4、8、12周，糖尿病对照组和罗格列酮治疗组大鼠血糖水平均明显高于正常对照组，差异均有统计学意义（P〈O．01），罗格列酮治疗组与糖尿病对照组大鼠血糖相比，差异均无统计学意义（q=0．81、0．82、1．23，P〉O．05）。正常对照组大鼠视网膜结构完整、排列规则，糖尿病对照组大鼠视网膜细胞水肿，排列紊乱，但罗格列酮治疗组大鼠视网膜结构接近正常。正常对照组大鼠视网膜中NF—KBp65呈弱表达，糖尿病对照组和罗格列酮治疗组大鼠视网膜NF-κBp65蛋白的表达（A值）均较正常对照组明显增加，差异均有统计学意义（P〈O．01）；给药后8周和12周时，罗格列酮治疗组大鼠视网膜NFBackground As one of the most common microvascular complication of diabetes in eyes, diabetic retinopathy （DR） is one of the most important cause of blindness. Nuclear factor-kappa B （NF-κB） is involved in the occurrence and development of the disease through the activation of a series of inflammatory cytokines. Objective The present study was to investigate the effects of peroxisome proliferator-activated receptor-gamma （PPAR-γ） excitomotor, rosiglitazone, on NF-κB expression and apoptosis of the retinal ganglion cells （RGCs）in the retina with diabetes mellitus. Methods Ninety SPF male Wistar rats were randomized into normal control group, diabetic control group and rosiglitazone group. Diabetes mellitus was induced by intraperitoneal injection of 50 mg/kg streptozotocin （STZ）. Then 3 mg/kg rosiglitazone was intragastricly administered once per day in the rosiglitazone group, and the same volume of saline solution was used at the same way in the normal control group and diabetic control group from 3 days after modeling. The rats were sacrificed and the eye cups specimen was made at 4,8 and 12 weeks after usage of drugs. Retinal histopathologieal examination was performed by hematine-eosin staining, and expression of NF-κB p65 protein in retina and apoptotic index（AI） of RGCs were detected by immunohistoehemistry and TUNEL assay, respectively in different time points mentioned above. The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State and Technology Commission. Results The blood glucose level was significantly elevated at various time points in the diabetic control group and rosiglitazone group compared with normal control group（ P〈O. 01 ） , and that of the rosiglitazone group was significantly declined in comparison to the diabetic control group （ q = 0. 81, 0. 82 ,1. 23 , P〉0.05 ）. Normal retinal structure was seen in the normal control group,and edema retinal cell and disorder of retinal layers w

关 键 词：过氧化物酶体增生物激活受体-γ激动剂 糖尿病视网膜病变 视网膜神经节细胞 核因子-κB 凋亡 

分 类 号：R965[医药卫生—药理学]