注射用盐酸多西环素对兔角膜新生血管的抑制作用  

Inhibitory effects of doxycycline on rabbit corneal neovascularization

作　　者：马为梅[1] 李春花[1] 雷晓琴[1] 周云云 MA Wei-Mei;LI Chun-Hua;LEI Xiao-Qin;ZHOU Yun-Yun(Department of Ophthalmology,Xi’an No.4 Hospital,Xi’an 710004,Shaanxi Province,China)

机构地区：[1]西安市第四医院,陕西省西安市710004

出　　处：《眼科新进展》2018年第12期1123-1128,共6页Recent Advances in Ophthalmology

基　　金：陕西省科技厅社会发展科技攻关项目(编号:2015SF232;2015SF085);西安市科技局社会发展引导计划-医学研究项目[编号:SF1513(3)]~~

摘　　要：目的研究基质金属蛋白酶抑制剂盐酸多西环素对兔角膜新生血管(corneal neovascularization,CNV)生长的影响。方法成年大耳白兔33只(66眼),随机分为对照组、碱烧伤组和多西环素组。对照组3只(6眼)不做处理。剩余30只(60眼)利用1 mol·L^(-1)Na OH滤纸片建立双眼碱烧伤模型,右眼为多西环素组,左眼为碱烧伤组。碱烧伤组不给予药物治疗,多西环素组隔日结膜下注射0.1 m L注射用盐酸多西环素(10 g·L^(-1))。观察兔CNV的生长情况,应用免疫组织化学化法检测角膜组织中血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)、组织型金属蛋白酶抑制剂-2(tissue inhibitors of metalloproteinase-2,TIMP-2)的表达情况。结果造模后3 d,可见碱烧伤组和多西环素组CNV长入透明角膜。造模后4 d、7 d、14 d、21 d,多西环素组CNV的面积分别为(6.15±2.85) mm^2、(14.39±4.04) mm^2、(18.07±5.74) mm^2、(19.44±6.95) mm^2,碱烧伤组CNV的面积分别为(17.00±4.60) mm^2、(37.93±6.91) mm^2、(42.25±9.32) mm^2、(38.81±4.87) mm^2,各时间点多西环素组CNV的面积均明显小于碱烧伤组(均为P <0.05)。造模后1 d、4 d、7 d、14 d、21 d,多西环素组角膜上皮层VEGF灰度值分别为167.74±10.59、140.14±12.14、128.69±9.21、103.06±8.29、176.16±9.72,碱烧伤组角膜上皮层VEGF灰度值分别为129.79±10.97、100.51±21.73、81.38±9.98、62.54±10.30、148.81±8.65,造模后各个时间点多西环素组VEGF的表达均明显少于碱烧伤组(均为P <0.05)。造模后4 d、7 d、14 d,多西环素组角膜上皮层MMP-2灰度值分别为83.50±14.81、123.42±16.20、110.90±8.98,碱烧伤组角膜上皮层MMP-2灰度值分别为65.27±12.84、91.31±13.22、94.28±6.46,造模后4 d、7 d、14 d多西环素组角膜上皮层MMP-2表达均明显低于碱烧伤组(均为P <0.05)。造模后21 d,角膜上皮层TIMP-2的表达最强,但造模后多西环素组角膜上�Objective To explore the inhibitive effects of doxycycline on rabbit corneal neovascularization(CNV).Methods Totally 33 rabbits(66 eyes)were divided into three groups randomly:normal group,alkali-injured group,doxycycline group.There was no treatment for the 3 rabbits in control group.Corneas of 30 rabbits were injuried with 1 mol·L^-1 NaOH by filter paper for alkali-injured group and doxycycline group.Alkali-injured group treated with no drug.Doxycycline group received subconjunctival injection with 0.1 mL doxycycline solution(10 g·L^-1)every other day.The CNV was observed by slit lamp microscope.The expression of vascular endothelial growth factor(VEGF),matrix metalloproteinase-2(MMP-2),tissue inhibitors of metalloproteinase-2(TIMP-2)in corneal was measured by immunohistochemistry.Results At 4,7,14 and 21 day after injury,the CNV area indoxycycline group was(6.15±2.85)mm^2,(14.39±4.04)mm^2,(18.07±5.74)mm^2,(19.44±6.95)mm^2.The CNV area inalkali-injured group was(17.00±4.60)mm^2,(37.93±6.91)mm^2,(42.25±9.32)mm^2,(38.81±4.87)mm^2,The CNV area in doxycycline group was significantly less than that in alkali burn group at the time points(P<0.05).At 1,4,7,14 and 21 day after injury,the gray value of VEGF in corneal epithelial cells indoxycycline group was 167.74±10.59,140.14±12.14,128.69±9.21,103.06±8.29,176.16±9.72,and that in alkali-injured group was 129.79±10.97,100.51±21.73,81.38±9.98,62.54±10.30,148.81±8.65.The expression of VEGF in doxycycline group was lower than that in alkali-burn group at the time points(P<0.05).At 4,7 and 14 day after injury,the gray value of MMP-2 in doxycycline group was 83.50±14.81,123.42±16.20,110.90±8.98,and that in alkali-injured group was 65.27±12.84,91.31±13.22,94.28±6.46.The expression of MMP-2 in the corneal epithelial layer in doxycycline group was suppressed markedly compared with that in alkali-injured group(P<0.05).On the 21 day after injury,the expression of TIMP-2 in corneal epithelium cells was the strongest.The expression of TIMP-2 in corneal epi

关 键 词：角膜新生血管 多西环素 血管内皮生长因子 基质金属蛋白酶-2 组织型金属蛋白酶抑制剂-2 

分 类 号：R772.2[医药卫生—眼科]