[1]马为梅,李春花,雷晓琴,等.注射用盐酸多西环素对兔角膜新生血管的抑制作用[J].眼科新进展,2018,38(12):1123-1128.[doi:10.13389/j.cnki.rao.2018.0265]
　MA Wei-Mei,LI Chun-Hua,LEI Xiao-Qin,et al.Inhibitory effects of doxycycline on rabbit corneal neovascularization[J].Recent Advances in Ophthalmology,2018,38(12):1123-1128.[doi:10.13389/j.cnki.rao.2018.0265]
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注射用盐酸多西环素对兔角膜新生血管的抑制作用/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
38卷
期数:
2018年12期
页码:
1123-1128
栏目:
实验研究
出版日期:
2018-12-05

文章信息/Info

Title:
Inhibitory effects of doxycycline on rabbit corneal neovascularization
作者:
马为梅; 李春花; 雷晓琴; 周云云
710004　陕西省西安市，西安市第四医院
Author(s):
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
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
Keywords:
CNV; doxycycline; VEGF; MMP-2; TIMP-2
分类号:
R772.2
DOI:
10.13389/j.cnki.rao.2018.0265
文献标志码:
A
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-1NaOH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 mL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）mm2、（14.39±4.04）mm2、（18.07±5.74）mm2、（19.44±6.95）mm2，碱烧伤组CNV的面积分别为（17.00±4.60）mm2、（37.93±6.91）mm2、（42.25±9.32）mm2、（38.81±4.87）mm2，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皮层TIMP-2表达和碱烧伤组表达强度相似，两组比较差异无统计学意义（P>0.05）。结论　VEGF、MMP-2、TIMP-2在CNV发生发展中发挥着重要的调控作用，盐酸多西环素可通过抑制基质胶原纤维的降解来降低炎症反应，并通过抑制角膜碱烧伤后兔角膜组织中VEGF、MMP-2的表达，进而抑制CNV的发生发展。
Abstract:
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)mm2，(14.39±4.04)mm2，(18.07±5.74)mm2，(19.44±6.95）mm2.The CNV area inalkali-injured group was （17.00±4.60)mm2，(37.93±6.91)mm2，(42.25±9.32)mm2，(38.81±4.87）mm2，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 epithelium cells indoxycycline group was similar to that in alkali-injured group，there was no significant difference between two groups（P>0.05）.Conclusion　VEGF，MMP-2 and TIMP-2 play an important regulatory role in the occurrence and development of CNV.Doxycycline can inhibit the degradation of matrix collagen fibers，inhibits the inflammatory reaction and inhibits the expression of VEGF and MMP-2 in the corneal tissue of rabbits after corneal alkali burn，as a resulte it inhibits the occurrence and development of rabbit CNV.

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备注/Memo

备注/Memo:
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）］
更新日期/Last Update: 2018-12-04