重组人血管内皮抑制素注射液对激光诱导兔脉络膜新生血管的抑制作用  

Inhibitory effect of recombinant human endostatin on choroidal neovascularization in a rabbit model

作　　者：赵秀娟[1] 曲超[2] 樊映川[2] 

机构地区：[1]泸州医学院临床医学院眼科,646000 [2]四川省医学科学院 四川省人民医院眼科,成都610072

出　　处：《中华实验眼科杂志》2011年第12期1087-1091,共5页Chinese Journal Of Experimental Ophthalmology

基　　金：四川省出国留学人员资助项目（303005002082）、四川省医学科学院院课题资助项目（303005002017037）

摘　　要：背景脉络膜新生血管（CNV）是多种眼底病变的严重并发症。研究表明，重组人血管内皮抑制素能够阻断血管内皮生长因子（VEGF）的信号通路，并通过核仁素发挥体内外抗血管生成的效应。目的观察玻璃体腔内注射重组人血管内皮抑制素对激光诱导CNV的抑制作用。方法将8～12周龄的健康青紫蓝兔16只用随机数字表法分为模型组和重组人血管内皮抑制素组，所有动物用氩离子532nm绿激光机在视盘下方1—2DD处击射25点诱导实验性CNV模型，重组人血管内皮抑制素组于光凝后1周玻璃体腔内注射给药。2组兔均于造模后1、2、4周行荧光素眼底血管造影（FFA）和光学相干断层扫描（OCT）检查，并于造模后2周、4周摘除眼球制作视网膜切片，用苏木精-伊红染色法行视网膜组织病理学检查。收集动物玻璃体和血清，用ELISA法检测VEGF和色素上皮衍生因子（PEDF）质量浓度。结果眼底检查表明激光光凝后1周即出现视网膜水肿和渗出，光凝后第4周可见光凝点周围的灰黄色瘢痕。FFA检查显示，光凝后1周42％（84／200）的光斑在脉络膜期和动脉早期出现高荧光团，造模后2周重组人血管内皮抑制素组荧光素渗漏少于模型组，造模后4周渗漏几乎消失。OCT检查显示，兔眼光凝后1周激光斑下方的视网膜色素上皮（RPE）下出现团块状、梭形或不规则膨大的局部强反射区，其间可见条带状或片状红白色高密度反光；光凝后各时间点重组人血管内皮抑制素组OCT检查可见部分CNV闭塞，愈合早，瘢痕较小。视网膜组织病理学检查表明，重组人血管内皮抑制素组光凝区视网膜结构的损伤表现比模型组CNV发展迟缓。重组人血管内皮抑制素组各时间点血清PEDF的质量浓度均明显高于模型组（P〈0．01），各时间点玻璃体及血清VEGF／PEDF比值模型组均高于重组人血管内皮抑制素组（P〈0�Background Choroidal neovascularization （CNV） is a serious complication of many fundus diseases. A variety of factors are associated with CNV. Research showed that recombinant human endostatin （ rh-endostatin） can arrest the vascular endothelial growth factor （VEGF） pathway and inhibit the proliferation of endothelial ceils and angiogenesis. Objective This study was to observe the inhibition of rh-endostatin on experimental CNV. Methods The CNV animal models were created by Argon laser with the wavelength 532 nm to irradiate the inferior retina away optical disc 1-2 DD for 25 spots in 32 eyes of 16 chinchilla rabbits. The laser parameters were as follows： power 800 mW, spot diameter 75 Ixm and time shutter 50 ms. The models were then divided into model control group and rh-endostatin group. Rh-endostatin was intravitreously injected via scleral incision in 16 eyes of 8 model rabbits at 1 week after photocoagulation. Fundus fluorescein angiography（FFA） and optical coherence topography（OCT） were performed at 1,2,4 weeks after photocoagulation respectively. The eyeballs were enucleated and the retinal sections were prepared for the histopathological examination, and the contents of VEGF and pigment epithelial derived factor （PEDF） in rabbit vitreous, and blood serum were detected by ELISA at 2,4 weeks after photocoagulation. Results Retinal edema and exudes were seen in 1 week and scarring in 4 weeks after photoeoagulation. In rh-endostatin injection group, the hyperfluorescence masses were seen in the background phase and early arterial phase in 42% （84/200） of spots in the first week. The fluorescence leakage was decreased in the rh-endostatin injection group compared with control group in the second week and ceased at the third week on the FFA after injection. Variety forms of hyperreflective zones were found below the retinal pigment epithelium on the seventh day after photocoagulation. But the partial vessel occlusion and fibroplasias were identified in the rh-endostatin injection

关 键 词：脉络膜新生血管 人血管内皮抑制素 动物模型 氩激光 

分 类 号：R96[医药卫生—药理学]