塞内昔布抑制兔脉络膜新生血管的形成  

Celecoxib inhibits retinal vascular endothelial growth factor expression and vascular leakage in an experimental model of Krypton laser-induced choroidal neovascularization in the rabbits

作　　者：乔岗[1] 周希瑗[1] 邓鑫[1] 李琳[1] 

机构地区：[1]重庆医科大学第二临床学院眼科,重庆400010

出　　处：《眼视光学杂志》2005年第4期257-260,共4页Chinese Journal of Optometry & Ophthalmology

摘　　要：目的利用激光诱导的脉络膜新生血管(choroidal neovascularization,CNV)兔模型,研究CNV的发生机制以及特异性环氧化酶(cycloxygenase,COX)-2抑制剂对其有无抑制作用,为临床上与脉络膜新生血管相关眼病的防治提供一种思路.方法健康有色家免20只,随机分为4组,包括空白对照组、实验对照组、塞内昔布(Celecoxib)治疗组、消炎痛治疗组,各5只兔10只眼.给药组通过灌胃法分别给药(塞内昔布100 mg/d·只,消炎痛25 mg/d·只),1周后除空白对照组外的15只兔(30只眼)均经散瞳、麻醉后,以波长647 nm的氪红激光(光斑直径为50 μm,功率为0.7 W,时间为0.1 s),在距视盘2～3个视盘直径的颞侧髓线上下视网膜处密集照射20个点,光斑间隔300 μm用以复制CNV兔模型.各组家兔分别于光凝后第3天、第1周、第2周、第3周,第1个月进行眼底荧光造影(fluorescein fundus angiography,FFA)及脉络膜造影(indocyanine green angiography,ICGA).再从各组中随机选取一只动物处死,摘除眼球取眼后段组织固定、包埋,制5～7 μm切片.用常规HE染色及用免疫组化(S-P法)分别检测COX-2和血管内皮生长因子(vascular endothelial growth factor,VEGF)在视网膜和脉络膜中的表达.结果光凝后第7天出现CNV,兔眼光凝斑CNV发生率高(占63%),眼底造影和光镜下均有相应改变.光凝后对各组FFA/ICGA进行比较,CNV发生率差异有显著性(P<0.05).各组视网膜上均有COX-2和VEGF的表达,两者表达趋势一致,空白对照组呈弱阳性, 实验对照组表达呈强阳性 ( P < 0.01),给药组呈弱阳性(P>0.05),其中Celecoxib组几乎不表达.COX-2主要定位于神经节细胞和外丛状层,VEGF主要定位于神经节细胞、内核层和血管内皮细胞.结论 COX-2和VEGF在正常及实验干预兔视网膜上均有表达,通过预防性服用特异性环氧化酶-2抑制剂(Celecoxib)可减少COX-2和VEGF的表达,两者变化趋势基本一致,提示COX-2可能为VEGF的上游调节因子.通�Objective To evaluate the effect of Celecoxib , a selective cycloxygenase-2（COX-2） inhibitor, inhibits retinal vascular endothelial growth factor（VEGF）, COX-2 expression and vascular leakage, with argon laserr-induced choroidal neovaseularization （CNV） model in the pigmental rabbits. Methods 20 healthy colored rabbits were divided into 4 groups： laser group, Celecoxib group, indomethacin group and control group. Each group has 5 rabbits （10 eyes）. Celecoxib was administered B.i.d. by oral garage （50 mg/kg） and indomethacin by oral also （25mg/d）. Experimental eyes in 15 rabbits were. received a series of 20 argon green laser （647 nm） lesions per eye （0.7 W, 50μm, 0.1 s）. Fundus fluorescein angiography （FFA） and indocyanine green angiography （ICGA） were performed, then the rabbits were terminated immediately. The eyes were enucleated and processed for histopathologic and immunohistochemistry examination on the 3rd day, 7th day, 14th day, 21st day,30th day.Ressults CNV was firstly appeared on day 7 after photocoagulation, reaching the peak on the 21st day.The incidence of CNV was 63.0%. Disciform leakage staining appeared in the FFA. The immunohistochemistry examination of VEGF and COX-2 were positive in retina from the 2nd week after photocagulation, and they had the same change trend. Conulusion The present studies demonstrated that celecoxib cannot block CNV induced by laser photocoagulation but it can reduce the express of VEGF and incidence of CNV.

关 键 词：脉络膜新生血管/药物疗法 塞内昔布/治疗应用 血管内皮生长因子 

分 类 号：R96[医药卫生—药理学]