摘要
目的建立模拟人类增殖型糖尿病性视网膜病变(proliferative diabetic retinopathy,PDR)的动物模型,并确证其价值。方法链脲佐菌素(streptozotocin,STZ)60 mg/kg腹腔注射造成SD大鼠糖尿病模型1个月后行VEGF玻璃体注射制造增殖型糖尿病眼底病变模型(C组),观察造模后不同时间荧光素眼底血管造影(fluorescence fundus angiography,FFA)改变及有无CD105标记阳性的视网膜毛细血管内皮细胞,并与传统的非增殖型糖尿病眼底病变大鼠模型(B组)作比较。结果 FFA结果显示:正常组无1例观察到异常荧光;B组大鼠仅观察到背景荧光的增强;C组大鼠不仅出现了背景荧光增强、大血管扭曲和毛细血管扩张、视网膜血管荧光素渗漏、视网膜内出血等临床中常见的非增殖期病变,还观察到了视网膜新生血管这种增殖期糖尿病性视网膜病变特有的体征。光镜观察视网膜血管渗漏情况及免疫组化CD105标记视网膜内增殖的新生血管内皮细胞情况显示:正常组及B组大鼠无1例视网膜微血管碳素颗粒渗漏,CD105均为阴性;C1组(VEGF玻璃体注射后2周):仅观察到神经节细胞层大血管有碳素颗粒的渗漏,CD105阴性;C2组(VEGF玻璃体注射后4周):除C1组病变外,还可观察到外核层有渗漏至血管外的碳素颗粒,CD105阳性;C3组(VEGF玻璃体腔注射后8周):除C2组病变外,还可观察到黄斑区水肿、渗出等病理改变、广泛的微血管渗漏,CD105阳性。结论该动物模型成功地观察到视网膜新生血管,并与出现增殖内皮细胞的病程一致,经FFA及免疫组化CD105标记验证有很好的应用价值,并且周期短、更经济,为临床筛选药物研究提供了理想动物模型。
Objective To establish a rat model of human proliferative diabetic retinopathy（PDR）,and to assess its value in order to provide an ideal animal model for clinical neotype drug research.Methods Diabetic Sprague-Dawley（SD） rats were intravitreously injected with VEGF at 1 month after receiving intra-peritoneal injection of 60 mg/kg body weight of streptozotocin（STZ）（C group）.The fluorescence fundus angiographic（FFA） changes and CD105-positive retinal vascular endothelial cells were observed by light microscopy at different time points after VEGF injection.The results were compared with the SD rats only received intraperitoneal injection of 60 mg/kg body weight of STZ（B group）.Results The FFA results showed that no abnormal fluorescence was observed in the normal rats and only enhanced background fluorescence was observed in the B group.However,not only the non-proliferative pathological changes such as enhanced background fluorescence,retinal great vessel buckling,angiotelectasis,retinal vascular leakages and hemorrhage,but also the proliferative pathological changes of diabetic retinopathy such as intraretinal new vessels were observed in the C group.Retinal vascular leakage of carbon granules and CD105-positive retinal vascular endothelial cells were not observed in the normal rats and the B group.In the C1 group（two weeks after VEGF injection）,carbon granules leakage was only observed in the great vessels of ganglion cell layer,but there were no CD105-positive retinal vascular endothelial cells observed.In the C2 group（four weeks after VEGF injection）,carbon granules leakage was observed in outer nuclear layer,and CD105-positive retinal vascular endothelial cells were also observed besides the pathological changes of the C1 group.In the C3 group（eight weeks after VEGF injection）,far-reaching carbon granules leakage was observed as well as macular edema and exudation,and CD105-positive retinal vascular endothelial cells were also observed besides the pathological changes of the C2 group.Conclusion The PDR rat model is successfully established,which is proved to have good application value by FFA and CD105 immunohistochemistry.The CD105-positive vascular endothelial cells observed by light microscopy coincide with the intraretinal new vessels observed by FFA at the same time.Therefore,we provide an ideal animal model for clinical studies on drug screening.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2012年第12期1218-1222,共5页
Journal of Third Military Medical University
