酪氨酸激酶抑制剂E7080治疗大鼠脉络膜新生血管的实验研究  

Effect of tyrosine kinase inhibitor E7080 on laser induced choroidal neovascularization in rat

作　　者：张敬学 闫雪静 刘谦 武珅 Zhang jingxue;Yan Xuejing;Liu Qian;Wu Shen(Beijing Tongren Eye Cener,Beijing Tongren Hospital,Capital Medical University,Beijing Institute of Ophthalmology,Beijing Ophthalmology&Visual Sciences Key Lab.,Beijing 100730,China)

机构地区：[1]首都医科大学附属北京同仁医院,北京同仁眼科中心,北京市眼科研究所,北京市眼科学与视觉科学重点实验室,100730

出　　处：《中华眼科医学杂志（电子版）》2020年第4期219-225,共7页Chinese Journal of Ophthalmologic Medicine(Electronic Edition)

基　　金：国家重点研发计划(2017YFA0104102);北京市属医学科研院所公益发展改革试点项目(京医研2018-2);北京市医院管理中心"青苗"计划(QML20180208)。

摘　　要：目的探讨酪氨酸激酶抑制剂E7080对实验大鼠脉络膜新生血管(CNV)的抑制作用。方法成年雄性棕色挪威大鼠60只,由北京维通利华实验动物公司提供。采用数字表法将大鼠随机分为对照组、E7080低剂量组(10 mg·kg^-1·d^-1)及E7080高剂量组(20 mg·kg^-1·d^-1),每组各20只。采用激光诱导实验大鼠形成CNV,以完成动物模型的制作。7 d后,按不同分组给药干预。分别于造模后7 d及给药后7 d、14 d采用荧光素眼底血管造影检查CNV形成与荧光渗漏的情况。分别于给药后7 d和14 d,采用组织病理学的方法评估CNV的病理情况。分别于造模后7 d及给药后14 d,采用视网膜色素上皮层-脉络膜-巩膜复合体铺片植物凝集素B4染色观察CNV的面积。CNV荧光信号的强度、CNV荧光信号的厚度以及凝集素B4染色的CNV面积,以均数±标准差进行描述。多组样本间不同组间均数的比较,采用重复测量资料的方差分析,采用LSD检验进行两两比较。结果荧光素眼底血管造影的检查结果显示,给药7 d后,低剂量组和高剂量组实验大鼠CNV相对渗漏荧光信号的强度分别为(0.5378±0.0967)和(0.3774±0.086),均低于对照组的(0.6752±0.095),差异具有统计学意义(t=6.342,13.99;P<0.05);给药14 d后,低剂量组和高剂量组的CNV相对渗漏荧光信号强度分别为(0.5735±0.0726)和(0.4071±0.1197),也均低于对照组(0.7305±0.0924),差异有统计学意义(t=6.92,14.50;P<0.05)。苏木精-伊红染色结果显示,药物处理7 d后,低剂量组和高剂量组的CNV厚度分别为(84.14±8.829)μm和(77.23±9.365)μm,均低于对照组的(125.3±18.18)μm,差异具有统计学意义(t=7.38,8.628;P<0.05);药物处理14 d后,低剂量组和高剂量组的CNV厚度分别为(86.21±10.51)μm和(77.88±7.39)μm,均低于对照组的(147.9±19.66)μm,差异具有统计学意义(t=9.656,10.44;P<0.05)。视网膜色素上皮层-脉络膜-巩膜复合体铺片荧光染色显示,低剂量组和高剂量组实�Objective The aim of this study was to expolre the effect of tyrosine kinase inhibitor E7080 on laser-induced choroidal neovascularization in rats.Methods Sixty adult male brown Norway rats were provided by Beijing Vital River Laboratory Animal Technology Co.Ltd.They were randomly divided into control group,E7080 low-dose(10 mg·kg^-1·d^-1)group,and E7080 high-dose(20 mg·kg^-1·d^-1)group according to random number table.The choroidal neovascularization was induced by fundus laser photocoagulation.The drug was applied at seven days after laser photocoagulation.Fundus fluorescein angiography was used to check choroidal neovascularization formation and fluorescence leakage at 7 days after laser photocoagulation,7 days and 14 days after drug administration.The histology of choroidal neovascularization was assessed by histopathological examination at 7 days and 14 days after administration.The area of choroidal neovascularization was observed by staining isolectin B4 on RPE-choroid-sclera flat mounts.The CNV fluorescence signal intensity,thickness and CNV area stained with lectin B4 s were statistically described as mean±standard deviation(Mean±SD).The comparison of the mean between different groups among multiple samples adopts repeated measures analysis of variance,and LSD test was used for pairwise comparison.Results FFA showed that after 7 days of administration,the relative leakage fluorescence signal intensity of CNV in the low-dose group and the high-dose group were(0.5378±0.0967)and(0.3774±0.086)respectively,which were lower than those of the control group(0.6752±0.095);the difference was statistically significant(t=6.342,13.99;P<0.05);14 days after administration,the relative leakage fluorescence signal intensity of CNV in the low-dose group and the highdose group were(0.5735±0.0726),(0.4071±0.1197),also lower than the control group(0.7305±0.0924);the difference was statistically significant(t=6.92,14.5;P<0.05).The results of hematoxylin-eosin staining showed that after 7 days of drug treatment,the

关 键 词：脉络膜新生血管 酪氨酸激酶抑制剂 小分子药物 渗出性年龄相关性黄斑变性 

分 类 号：R773.4[医药卫生—眼科]