两种缺血性眼病大鼠模型的建立和比较研究  

Establishment and Comparison of Two Rat Models of Ischemic Ophthalmopathy

作　　者：谭为 袁天翊 周茂杰 王建美 顾政一 杜冠华 TAN Wei;YUAN Tianyi;ZHOU Maojie;WANG Jianmei;GU Zhengyi;DU Guanhua(School of Pharmacy,Xinjiang Medical University,Urumqi 830011;Beijing Key Laboratory of Drug Target Identification and Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050;Xinjiang Institute of Materia Medica,Urumqi 830004)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830011 [2]中国医学科学院药物研究所,北京市药物靶点研究与新药筛选重点实验室,北京100050 [3]新疆维吾尔自治区药物研究所,乌鲁木齐830004

出　　处：《中药药理与临床》2023年第9期76-84,共9页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家重点研发计划(编号:2020YFC2008302);国家自然科学基金(编号:82141204);中国医学科学院医学与健康科技创新工程重大协同创新项目(编号:2021-I2M-1-005、2022-I2M-JB-010)。

摘　　要：目的:对比低氧诱导和血栓诱导这两种缺血性眼病的大鼠模型差异。方法:分别建立低氧诱导的眼缺血模型和一种新型的电凝法诱导微小血栓阻塞眼部血管的眼缺血模型,运用虹膜拍照、眼底视网膜显微成像技术、光学相干断层扫描技术(OCT)、视觉电生理(f-ERG)技术、组织病理学技术,多学科、多角度对比这两种模型的差异。结果:低氧诱导的缺血性眼病模型中,眼组织缺氧后,角膜变薄,上皮层增厚,血管膜、视网膜血管以及视网膜结构因缺氧而水肿,内核层、外丛状层均增厚而内丛状层反而变薄;视杆细胞反应中的b波振幅异常升高,视锥细胞反应中的b波振幅明显下降。而血栓诱导的缺血性眼病模型中,缺血后的角膜基质层结构紊乱,基质细胞丢失,内皮细胞缺失;虹膜血管出现血栓和断流;睫状体细胞排列紊乱和水肿;视网膜厚度变薄,内丛状层、外核层和内核层均变薄,内核层细胞减少,光感受器结构改变,视网膜周细胞与内皮细胞丢失导致视网膜微血管结构明显萎缩,脉络膜因缺血而变薄并呈空泡样改变;而视杆细胞反应、视锥细胞反应以及闪烁反应均显示b波振幅下降,震荡电位、最大混合反应的振幅也明显下降。结论:这两种模型的病理表征不同,但是都可以造成血-视网膜屏障和血-房水屏障的损伤。这两种模型制备方法简单、病理过程可控、动物死亡率低、可重复性高,适合作为缺血性眼病药物评价的动物模型,为研究缺血性眼病选择合适的动物模型提供参考。Objective:To compare the two rat models of ischemic ophthalmopathy induced by low oxygen and thrombus,respectively.Methods:Two rat models of ischemic ophthalmopathy were established by low oxygen and a novel electrocoagulation-induced ocular microthrombus obstruction,respectively.The two models were compared in a multidisciplinary and multifaceted manner by iris photography,fundus retinal imaging,optical coherence tomography(OCT),visual electrophysiology(f-ERG),and histopathological techniques.Results:After low oxygen treatment,the ocular tissue presented thinned cornea,thickened epithelial layer,edematous vascular membrane,retinal vessels,and retinal structure,thickened inner nuclear layer and outer plexiform layer,and thinned inner plexiform layer.In addition,the b-wave amplitude in the response of rod cells abnormally increased,while the b-wave amplitude in the response of cone cells significantly decreased.In the thrombus-induced model of ischemic ophthalmopathy,the corneal stromal layer presented disarrangement,with loss of stromal cells and endothelial cells.In addition,the ocular tissue showed thrombosed and disconnected iris vasculature,disorganized and edematous ciliary body cells,thinned retina,inner plexiform layer,outer nuclear layer,and inner nuclear layer,reduced cells in the inner nuclear layer,changed photoreceptor structure,retinal microvasculature atrophy due to the loss of retinal pericytes and endothelial cells,and thinned and vacuolated choroid due to ischemia.Moreover,the b-wave amplitude,oscillatory potential,and maximal mixed response was significantly decreased in the rod cell response,cone cell response,and flicker response.Conclusion:Although the two modeling methods lead to different pathological representations,both can cause damage to the blood-retina barrier and the blood-aqueous humor barrier.With simple operation,controlled pathological processes,low animal mortality,and high reproducibility,the two modeling methods are suitable for the drug evaluation of ischemic ophthalmopathy,p

关 键 词：缺血性眼病 动物模型 低氧诱导 血栓诱导 血-视网膜屏障 血-房水屏障 

分 类 号：R771[医药卫生—眼科] R-332[医药卫生—临床医学]