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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:1d小剂量治疗组(C1组,9只),1d大剂量治疗组(C2组,9只),14d小剂量治疗组(C3组,9只),14d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(25mg/ml),小剂量组0.1ml,大剂量组0.2ml。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、28d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、28dC1和C2组均较B组明显减轻(P<0.01),28d时C3、C4组较B组明显减轻(P<0.01);28d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、28d时,C1、C2组均低于B组(P<0.01);28d时C3、C4组均低于B组(P<0.01);28d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。
Objective: To observe the therapeutic effect of Bevacizumab (Avastin) subconjunctival injection on the corneal neovascularization (CNV) model in rabbits. Methods: Forty-eight New Zealand white rabbits were randomly divided into three groups: normal control group (group A, n = 3), model group (group B, n = 9) and Bevacizumab treatment group (group C, n = 36) Were divided into 4 groups: 1d low dose treatment group (C1 group, 9 rats), 1d high dose treatment group (C2 group, 9 rats), 14d low dose treatment group (C3 group, 9 rats), 14d high dose treatment group C4 group, 9). The CNV models were prepared by corneal suture method in group B and group C. Bevacizumab (25mg / ml) was injected subconjunctivally into eyeballs at the corresponding time points in group C, and 0.1ml in the low dose group and 0.2ml in the high dose group. The corneal CNV growth was observed daily and the area of the cornea was calculated. The rabbits were photographed and recorded at 7, 14 and 28 days after modeling. The expression of VEGF was detected by immunohistochemistry in each group. VEGF content. Results: The growth of CNV: Compared with group B, the levels of C3 and C4 in group C and C4 were significantly decreased (P <0.01) (P <0.01). The C2 group was significantly lower than the C4 group (P <0.01). VEGF expression in corneal tissue and VEGF in aqueous humor: Group B gradually increased over time, and was positively correlated with the area of CNV (P <0.01). At 7, 14 and 28 days, the levels of VEGF in group C1 and C2 were lower than those in group B (P <0.01). The levels of C3 and C4 were lower than those of group B on the 28th day (P <0.01). There was no significant difference in CNV area, corneal and aqueous VEGF levels between C1 and C2 groups and between C3 and C4 groups. CONCLUSION: Bevacizumab can inhibit the growth of CNV in subconjunctival injection. The effect of Bevacizumab on the expression of VEGF and the level of VEGF in aqueous humor may be related to its effect.