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Bevacizumab(Avastin)抑制兔眼角膜新生血管的实验研究
章玉群,彭清,赵培泉*
0
(上海交通大学医学院附属新华医院眼科,上海 200092)
摘要:
目的:观察Bevacizumab(Avastin) 球结膜下注射对兔眼角膜新生血管(corneal neovascularization,CNV)模型的治疗作用。方法:新西兰大白兔48只,随机分为正常对照组(A组,3只)、模型组(B组,9只)和Bevacizumab(Avastin)治疗组(C组,36只),C组又再次分为4组:1 d小剂量治疗组(C1组,9只),1 d大剂量治疗组(C2组,9只),14 d小剂量治疗组(C3组,9只),14 d大剂量治疗组(C4组,9只)。B组和C组采用角膜缝线法制备CNV模型,C组分别在相应时间点眼球结膜下注射Bevacizumab(25 mg/ml),小剂量组0.1 ml,大剂量组0.2 ml。术后每天观察兔眼角膜CNV生长情况并计算其面积,且于建模后7、14、28 d分别拍照记录,免疫组化方法检测各组角膜组织中VEGF的表达情况,ELISA法检测房水内VEGF含量。结果:CNV生长情况:7、14、28 d C1和C2组均较B组明显减轻(P<0.01),28 d时C3、C4组较B组明显减轻(P<0.01);28 d时C1组较C3组明显减轻(P<0.01),C2组较C4组明显减轻(P<0.01)。角膜组织中VEGF表达和房水中VEGF含量:B组随时间推移逐渐增高,且与CNV面积大小呈正相关(P<0.01);7、14、28 d 时,C1、C2组均低于B组(P<0.01);28 d时C3、C4组均低于B组(P<0.01);28 d时C1组低于C3组(P<0.01),C2组低于C4组(P<0.01)。C1和C2组之间以及C3和C4组之间在CNV面积、角膜和房水中VEGF水平方面均无显著差异。结论:球结膜下注射Bevacizumab可抑制CNV生长,且早期用药比晚期用药疗效更加显著,Bevacizumab的作用可能与其下调角膜组织VEGF的表达及房水中的VEGF含量有关。
关键词:  Bevacizumab  角膜新生血管化  血管内皮生长因子  角膜  眼房水
DOI:10.3724/SP.J.1008.2009.0907
投稿时间:2009-04-02修订日期:2009-07-14
基金项目:上海市重点学科建设项目(S30205).
Bevacizumab (Avastin) inhibits corneal neovascularization in rabbits
ZHANG Yu-qun,PENG Qing,ZHAO Pei-quan*
(Department of Ophthalmology,Xinhua Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200092,China)
Abstract:
Objective:To evaluate the effect of subconjunctival injection of Bevacizumab (Avastin) on corneal neovascularization(CNV) in rabbits.Methods: Forty-eight New Zealand rabbits were randomly divided into three groups:normal control group (group A,3 rabbits),neovascularization group (group B,9 rabbits) and Bevacizumab treatment group (group C,36 rabbits).Group C was further divided into group C1 (1 day small dose group) ,C2 (1 day high dose group),C3 (14 days small dose group) and C4 (14 days high dose group),with 9 rabbits each group.CNV model was made by suture in group B and C.Animals in group C were injected subconjunctivally with 0.1 ml or 0.2 ml Bevacizumab(25 mg/ml) in the left eyes.The growth of CNV was observed every day after operation and the neovascularization areas calculated.Expression of VEGF in the cornea was detected by immunohistochemistry on day 7,14 and 28 after suture.VEGF content in the aqueous humor was determined by ELISA assay.Results: CNV growth in group C1 and C2 was inhibited significantly compared with that in group B on day 7,14 and 28 (P<0.01).On day 28 the growth in group C3 and C4 was significantly inhibited compared with that in group B (P<0.01),that in group C1 was significantly inhibited than that in group C3,and that in group C2 was significantly inhibited compared with that in group C4 (P<0.01).VEGF levels in the cornea and aqueous humor in group B increased as time passed by,and they were positively associated with CNV area (P<0.01).On day 7,14,and 28,the VEGF levels in the cornea and aqueous humor in C1 and C2 groups were significantly lower than that in group B (P<0.01).On day 28,those in group C3 and C4 were significantly lower than those in group B (P<0.01);those in group C1 were significantly lower than those in group C3 (P<0.01);and those in group C2 were significantly lower than those in group C4 (P<0.01).The CNV area and VEGF levels in the cornea and aqueou humor were similar between C1 and C2 groups and between C3 and C4 groups.Conclusion: Subconjunctival administration of Bevacizumab can effectively inhibit corneal neovascularization in experimental CNV model,and early administration has a better outcome than late administration.Bevacizumab may exert its effect by down-regulating VEGF in cornea and aqueous humor.
Key words:  bevacizumab  corneal neovascularization  vascular endothelial growth factor  cornea  aqueous humor