Bevacizumab对大鼠角膜新生血管的抑制作用

Inhibitive effect of bevacizumab on corneal neovascularization in rats

目的观察bevacizumab对角膜新生血管的抑制作用。方法选取鼠龄6～8周、体质量(180±10)g的雄性Wistar大鼠40只,建立碱烧伤角膜新生血管模型;将大鼠随机分为3个不同剂量药物治疗组(实验组)和1个对照组,每组10只(20眼),大鼠角膜碱烧伤后分别给予结膜下注射不同剂量(0.5mg、1.0mg、2.0mg)的bevacizumab,对照组注入生理盐水;然后进行角膜新生血管的各项数据观察,观察期为16d,主要观察项目包括各组角膜新生血管的生长情况;计算角膜新生血管的生长面积;碱烧伤后第7天和第16天后采集角膜,标本行组织病理学检测和免疫组织化学检测,第16天,计算平均OD值;评价药物对角膜新生血管的抑制效果。结果碱烧伤后第7天、第14天,实验组与对照组新生血管面积比较差异均有统计学意义(均为P<0.05);组织病理学检测发现各实验组炎性细胞浸润、新生血管形成均明显轻于对照组。对照组血管内皮生长因子(vascular endothelial growth factor,VEGF)染色明显增强,实验组的表达明显减弱。碱烧伤后第16天,实验组与对照组比较,VEGF染色阳性细胞数和VEGF平均OD值差异均有统计学意义(均为P<0.05)。碱烧伤后第7天、第16天大鼠角膜CD34的免疫组织化学检测结果及新生血管密度计数方面,实验组和对照组比较差异均有统计学意义(均为P<0.05)。结论结膜下注射一定浓度的bevacizumab对大鼠角膜碱烧伤后的新生血管生长有抑制作用。

Objective To investigate the inhibitive effect of bevacizumab on corneal neovascularization（CNV）.Methods A total of 40 healthy male Wistar rats aged from 6 weeks to 8 weeks with weight mass（180±10）g were chosen and CNV animal models were established with alkali burn.The rats were randomly divided into 3 bevacizumab treatment groups with different concentrations and 1 control group,10 rats（20 eyes） in each group.The rats in treatment groups were subconjunctivally injected with bevacizumab at different dozes（0.5 mg,1.0 mg,2.0 mg） after alkali burn,respectively.Rats in control group received normal sodium.The data of CNV were observed for 16 days,mainly including the development of CNV in each group and areas of CNV.Cornea were collected on the 7th day and the 16th day after alkali burn,and detected by histopathologic and immunohistochemical examinations.The average OD value was calculated on the 16th day.The inhibitive effect of bevacizumab on CNV was evaluated.Results Compared with control group,areas of CNV in treatment groups had statistical differences on the 7th day and 14th day after alkali burn（all P0.05）.Histopathologic examination showed the infiltration of inflammation cells and condition of CNV in treatment groups were weaker than those in control group.Staining of vascular endothelial growth factor（VEGF） in CNV of control group was obviously increased,decreased in treatment groups.On the 16th day after alkali burn,VEGF positive cells and mean OD value of VEGF in treatment groups had statistical differences compared with control group（both P0.05）.On the 7th day and 16th day after alkali burn,the immunohistochemical results of CD34 in cornea and the CNV density counting in treatment groups had statistical differences compared with control group（all P0.05）.Conclusion Subconjunctival injection of bevacizumab with a certain concentration can inhibit the development of CNV after corneal alkali burn in rats.