摘要
目的观察精氨酸-甘氨酸-天门冬氨酸-丝氨酸(Arg-Cly-Asp-Ser,RGDS)肽对半导体倍频激光诱导的棕色挪威(BN)大鼠脉络膜新生血管(CNV)形成的抑制作用。方法选取27只 BN 大鼠通过半导体倍频激光(波长为532nm)眼底光凝方式建立 CNV 模型,另取3只 BN 大鼠作为正常对照。激光功率、光凝斑直径和曝光时间分别为525mw,50μm及0.05s。光凝后立即将27只模型大鼠随机分为3组,每组9只(18只眼)。分别为大剂量治疗组、小剂量治疗组和对照组,各组每只眼每天玻璃体腔内注射 RGDS 肽300、100和0μg,各组给药均持续7d。激光光凝后14d 各组大鼠均行眼底照相观察、荧光素眼底血管造影(FFA)和吲哚氰绿眼底血管造影(ICGA)检查。每组选取1只大鼠(2只眼)视网膜标本用透射电镜进行毒性观察,8只大鼠16只眼球标本分别行 FITC-右旋糖酐标记脉络膜巩膜铺片新生血管定量分析和组织病理学光镜、免疫组化观察,以评估 RGDS 肽对 CNV 的抑制效果。结果光凝后14d 对照组、小剂量治疗组、大剂量治疗组3组 FFA 检查中发现荧光渗漏且ICGA 检查证实 CNV 充盈的光凝斑所占百分率分别为69.4%、57.8%、38.9%。脉络膜巩膜铺片新生血管定量分析及组织学切片观察结果显示大剂量治疗组、小剂量治疗组脉络膜新生血管的形成与对照组相比均减少,差异有统计学意义(P<0.01)。一定剂量的 RGDS 肽能抑制脉络膜新生血管的生长,并呈剂量依赖关系。透射电镜结果提示玻璃体腔内注射 RGDS 肽对大鼠视网膜毒性不明显。结论 RGDS 肽可以抑制实验性脉络膜新生血管的形成,有望成为防治 CNV 的一种有效方法。
Objective To investigate the efficacy and feasibility of RGDS （Arg-Gly-Asp-Ser） peptide （an αv-integrin antagonist） in a rat model of laser-induced choroidal neovascularization （CNV）. Methods Experimental CNV was induced by laser photocoagulation in Brown Norway rats （50 μm diameter, 0.05 second duration and 525 mw intensity）. Phosphate buffered saline（PBS） or 100,300 μg of RGDS peptide in PBS were being injected intravitreally after laser surgery for 7 days. On the 14th day after photocoagulation, CNV was observed by fundus fluorescein angiography （FFA）and indocyanine green angiography（ICGA）. The area of CNV by high molecular weight FITC-dextran （MW 2 × 10^6） for high resolution angiography in RPE-choroid-sclera flat mounts and the thickness microscopically on histologic sections were evaluated. New vessels were detected and quantified by an-antibody against factor Ⅷ. Two eyes from each group were examined by transmission electron microscopy. Results In eyes with injections of 300 or 100 μg of RGDS peptide on the 14th day after laser photocoagulation, the development of CNV was significantly （ P 〈 0.01 ） inhibited showing by RPE-choroid-sclera flat mounts. Histologically, the thickness of the CNV lesions was significantly （ P 〈 0.01 ） reduced in eyes that received 300 or 100 p,g of RGDS peptide injection. Immunoreactivity of factor Ⅷ in CNV showed significant difference （ P 〈 0.01 ） in eyes injected with RGDS peptide compared with control eyes. The reduction of the area and the thickness of CNV by RGDS peptide were in a dose-dependent manner. No evidence of toxicity was found in retina by transmission electron microscopy in every group. Conclusions RGDS peptide effectively inhibits CNV progression in a rat model of laser-induced CNV, suggesting that this α-integrin antagonist may be beneficial in the treatment of CNV.
出处
《中华眼科杂志》
CAS
CSCD
北大核心
2006年第9期825-831,共7页
Chinese Journal of Ophthalmology
关键词
激光凝固术
脉络膜新生血管化
寡肽类
Laser coagulation
Choroidal neovascularization
Oligopeptides
