摘要
背景链脲佐菌素（STZ）诱导的1型糖尿病大鼠模型是目前公认的经典动物模型，常用于糖尿病视网膜病变（DR）的实验研究，但模型的制作多使用无色素大鼠的视网膜血管消化铺片技术，无法用荧光素眼底血管造影（FFA）进行活体动态观察，且实验中需要的动物数量较多。近年来有色素大鼠已逐渐用于制作DR模型，但采用活体动物FFA检测比较两种模型的研究较少。目的比较有色索大鼠和无色素大鼠糖尿病模型FFA和视网膜血管消化铺片的表现，选择适合活体监测视网膜血管改变的糖尿病模型大鼠品系。方法选择健康雄性Brown—Norway（BN）大鼠和Sprague—Dawley（SD）大鼠各15只，经尾静脉注射55mg／kg STZ制作1型糖尿病大鼠模型，注射后每周经鼠尾断端采血检测血糖，血糖值≥16．7mmol／L为造模成功。造模6周后选取大鼠右眼为实验眼，用裂隙灯显微镜观察模型鼠的眼前节变化，用眼底照相和FFA检查观察大鼠眼底血管变化，然后制备模型鼠离体视网膜血管消化铺片，过碘酸希夫染色后在光学显微镜下观察模型鼠视网膜血管的病理改变，比较2种不同品系大鼠视网膜血管在同样的病理改变下FFA的表现。结果造模后6周，共纳人造模成功的BN大鼠11只和SD大鼠10只，2种大鼠血糖分别为（24．73±2．98）mmol／L和（22．36±3．65）mmol／L，差异无统计学意义（t=7．873，P〉0．05）。BN大鼠组发生晶状体混浊者6眼，SD大鼠组5眼，差异无统计学意义（P=0．717）。FFA检查显示，BN大鼠组眼底在棕褐色背景下视网膜血管显影清晰，无脉络膜血管背景荧光干扰，9眼可见血管迂曲、荧光素渗漏等背景期糖尿病视网膜血管改变，而SD大鼠组由于脉络膜背景荧光和涡静脉的干扰，视网膜血管显影不清晰，未见背景期糖尿病视网膜血管改变。视网膜血管消化铺片显示，2种不同品系大鼠均被证实有视网膜毛细血管管径变化、周细胞数目的减少及血管内皮细胞数目的增加，BN大鼠组和SD大鼠组视网膜内皮细胞／周细胞（E／P）分别为11．50±3．68和12．86±3．94，差异无统计学意义（t=9．785，P〉0．05）。结论通过活体FFA观察，BN模型大鼠早期糖尿病视网膜血管改变的成像效果优于SD大鼠。
Background Streptozotocin （STZ）-induced type 1 diabetic model is an acceptable model and is often used to the study of diabetic retinopathy （ DR）. However, the model is often established using retinal digest preparation in vitro in albino rats, and therefore it is difficult to evaluate the change of retinal vessels by fundus fluorescein angiography （FFA） in vivo. Recently, pigmented rats are being used as the DR model. But the study on the comparison between albino rat model and pigmented rat model is seldom. Objective This study was to observe and compare the manifestations of FFA and retinal digest preparation in early diabetic pigmented diabetic rat and albino diabetic rat,and to select the right model of DR using FFA. Methods Type 1 diabetic models were induced in 15 six-week-old health male BN rats and 15 six-week-old health male SD rats by the injection of STZ （55 mg/kg） via tail vein. The models were thought to be successful in the rats with the blood glucose level ≥ 16.7 mmol/L. The right eyes of the rats were extracted 6 weeks after injection of STZ. Lens were examined by slit lamp microscope. Retinal vascular changes were examined by fundus photography, FFA and periodic acid Schiff staining of retinal digest preparation. The manifestations of FFA and retinal digest preparation were contrasted between BN rats and SD rats. The number of eyes with lens opaeification was compared by Chi-square test and the ratio of vascular endothelial ceils and perithelial ceils （E/P） was compared between BN rats and SD rats. The use and care of experimental animals complied the Statement of Ethic Committee of Tianjin Medicine University. Results Six weeks after injection of STZ, 11 BN rats and 10 SD rats were included in this study. The blood levels were （24.73±2.98）mmol/L and （22.36±3.65）mmol/L in BN rats and SD rats, respectively, without significant difference between the 2 types of rats （ t = 7. 873, P〉0.05 ）. Lens opaeifieation occurred in 6 BN rats and in 5 SD rats （P=0. 717）. FFA showed the clear retinal vascular under the brown background. Evident vessel disorder and fluorescence leakage like background stage of DR were seen in 9 eyes. However,in the SD rats,retinal vessel abnormality could not exhibited owing to the interference of ehoroid fluorescent light from ehoroidal vessels and vortex vein. Retinal digest preparation exhibited that unevenness of vessel diameter, decrease of perithelial cells and increase of endothelial cells in both types of rats. The E/P values were 11.50±3.68 in the BN rats and 12.86±3.94 in the SD rats,without significant difference between them （t = 9. 785 ,P〉0.05 ）. Conclusions The abnormality of fundus vascular morphology can be better displayed in pigmented diabetic rats than albino rats by FFA in vivo.
出处
《中华实验眼科杂志》
CAS
CSCD
北大核心
2014年第1期32-35,共4页
Chinese Journal Of Experimental Ophthalmology
基金
天津市教育委员会基金项目（20110224）
