贝伐单抗兔眼前房注射后在眼组织的分布及其不良反应的研究  

Distribution of bevacizumab in ocular tissue and its toxic effect after injection of anterior chamber

作　　者：刘琳[1,2] 马翔[1] 季艳丽[1] 冶卓[1] 

机构地区：[1]大连医科大学附属第一医院,116011 [2]怀化医学高等专科学校,418000

出　　处：《中华实验眼科杂志》2011年第10期884-889,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目（30471859）

摘　　要：背景贝伐单抗已被广泛用于眼部新生血管性疾病的治疗，对眼前房注射后其药代动力学改变和安全性评价可为其治疗虹膜新生血管和新生血管性青光眼提供依据。目的观察前房注射贝伐单抗后药物在兔眼组织的分布并评价其安全性。方法20只健康新西兰白兔按随机数字表法分为2组，实验组左眼前房注射0．05ml贝伐单抗（1．25mg），对照组左眼前房注射平衡盐溶液0．05ml。注射药物前后用裂隙灯及直接检眼镜检查眼前段和眼底表现并定期监测眼压、行角膜内皮镜检查并评估角膜内皮细胞计数的动态变化。前房注射后1、4、7、14、30d光学显微镜下行兔视网膜的组织病理学检查，注射后第4天和第30天透射电子显微镜下行兔视网膜的超微结构检查，应用免疫荧光染色法检测前房注射后不同时间贝伐单抗在眼组织中的分布情况。结果贝伐单抗前房注射后裂隙灯及直接检眼镜检查显示实验眼前后节组织和视网膜未见异常表现，实验组注药前后的眼压、角膜内皮细胞密度与对照组比较差异均无统计学意义（P=0．760，P=0．956）。眼组织病理学检查提示，实验组与对照组注药后角膜、晶状体、前房角、虹膜、睫状体、视网膜结构均未见异常改变；透射电子显微镜下实验组和对照组注药后角膜、晶状体、虹膜、睫状体超微结构无明显改变。免疫荧光染色显示，贝伐单抗前房注射后，注射眼和对侧眼的前房角、虹膜、睫状体、脉络膜和视网膜上均有红色荧光，对侧眼较注射眼荧光染色弱，红色荧光主要集中于血管壁和血管腔。贝伐单抗前房注射后第1天到第4天虹膜荧光染色最强，随后逐渐衰减，第30天仍有较弱的染色，注射后第7天睫状体染色较虹膜强，随后逐渐衰减，第30天仍有较弱的染色；注射后眼前房角染色最强的现象见于第4天到第7天，随后逐渐Background Bevacizumab has been widely used in the treatment of new blood vessel disease in ophthalmology. The investigation of the pharmacokineties and safety after intraeameral injection of bevacizumab can offer the basis for the management of iris neovascularization and neovascular glaucoma. Objective The present study was to observe the distribution of bevacizumab （avastin） in eye tissue and toxic effects following the injection of anterior chamber. Methods Twenty-four New Zealand albino rabbits were divided into two groups randomly. 0. 05 ml （1.25rag） of Bevacizumab was intracamerally injected into the left eyes in the experimental group, and a balanced salt solution of 0.05 ml was injected in the same way into the left eyes of the control group. The anterior segment of eyes and ocular fundus were examined by slit-lamp microscope and direct ophthalmoscope after injection. Intraocular pressure was measured and corneal endothelial microscopy was performed before and after the injections. Five rabbits of the two groups were sacrificed on the first day, the fourth day, the seventh day, the fourteenth day, and the thirtieth day after injection, and the eyeballs were enucleated for histopathological examination. The ultrastructure of eye tissue was observed under the transmission electron microscope on the fourth day and the thirtieth day, and then immunofluorescence staining were performed to assess the distribution of bevacizumab in the eye tissues. This experiment complied with the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission （Version 1988）. Results No abnormality in the cornea,lens, vitreous and retina was observed after the injection of bevacizumab under the slit lamp microscope and direct ophthalmoscope. No significant differences were found in intraocular pressure and corneal endothelial cell density in the bevacizumab group compared with the control group before injection and 2 hours, 1 day,7 days, 14 days, 30 days after

关 键 词：贝伐单抗 前房注射 血管内皮生长因子 免疫荧光染色 毒性作用 不良反应 

分 类 号：R77[医药卫生—眼科] R9[医药卫生—临床医学]