结膜下注射贝伐单抗对兔角膜新生血管的抑制作用

目的 观察碱烧伤后不同时间结膜下注射贝伐单抗（Bevacizumab）角膜新生血管（CNV）的形成与转归.方法 新西兰白兔54只,制成单眼碱烧伤模型,随机分为3组,每组18只眼,A组碱烧伤后结膜下立即注射贝伐单抗2.5 mg（0.1 ml）,B组碱烧伤后3d结膜下注射贝伐单抗2.5 mg（0.1 ml）,C组结膜下注射生理盐水0.1ml,为对照组.共观察28 d.裂隙灯显微镜下观察角膜新生血管生长情况,行眼前段照相并计算其面积,伤后7、14、28 d各组随机取6例角膜行共焦显微镜检查,观察角膜组织炎性细胞浸润情况及角膜新生血管形态学变化.结果 A、B及C组角膜新生血管开始出现的时间分别为（5.9＋0.8）d、（3.5＋0.6）d及（3.4＋1.1）d,其中A组明显较C组延长（P＜0.05）,B组与C组差异无统计学意义（P =0.068）.伤后各时间点A、B组角膜新生血管的生长面积均明显较C组减少（P＜0.05）,A组与B组角膜新生血管面积比较,差异有统计学意义（P＜0.05）.共焦显微镜检查可见C组烧伤区大量炎性细胞浸润及新生血管形成,而A组角膜炎性细胞较少,烧伤区无新生血管形成,B组见少量新生血管侵入烧伤区.3组基质层均可见纤维及瘢痕组织增生,其中治疗组纤维增生程度与瘢痕组织均较对照组轻.结论 结膜下注射贝伐单抗可抑制角膜炎性细胞形成,改善损伤角膜基质,促进角膜愈合,从而减少碱烧伤引起的角膜新生血管的生长,在早期注射能取得更好的疗效.

The inhibition effect of subconjunctival Bevacizumab on rabbit corneal neovascularization

Objective To evaluate the effect of subconjunctival bevacizumab on experimental corneal neovascularization （NV） in rabbits at different time points.Methods The right eyes of 54 white New Zealand rabbits were chemically burned with 1mol/L NaOH and randomly divided into three groups.Eighteen eyes （group A） received subconjunctival injection of bevacizumab （2.5 mg,0.1 mL） immediately after burn.Eighteen eyes （group B） received subconjunctival injection of bevacizumab （2.5 mg,0.1 mL） 3 days after burn with subconjunctival injection of normal saline.Group C was the control group.The angiogenesis and inhibition of corneal neovascularization were detected respectively by measuring the length and area of NV under slit lamp microscopy everyday.Corneal confocal microscope was used to detect the cornea at 7 days,14 days and 28 days after corneal burn.Results The occurrence time of corneal NV was （5.9± 0.8） d,（3.5 ± 0.6） d and （3.4 ± 1.1） d in group A,B and C.Compared with the group C,the corneal NV occurrence was significantly delayed in group A and B.No significant difference in the occurrence time of corneal NV was found between group B and group C （P =0.068）.The corneal NV areas of group A and group B were smaller than the group C at different time points,and the difference has statistical significance （P ＜ 0.05）.The degrees of fibrous structures and scars in corneal stroma of treatment groups were slightly less than the group C.Conclusion Subconjunctival injection of bevacizumab can sufficiently decrease the number of inflammatory cells in the cornea after chemical burn,improve the microenvironment of injured corneal stroma and accelerate the cornea wound healing,which eventually inhibit the growth of corneal NV.The anti-neovascular effect of bevacizumab is better if the injection is performed at the early stage of corneal angiogenesis.