贝伐单抗眼液对兔眼角膜新生血管抑制作用的实验研究  

Inhibition of corneal neovascularization with bevacizumab eye drops in rabbits

作　　者：常岩[1] 蔡莉[1] 王雨生[1] 王海燕[1] 李曼红[1] 

机构地区：[1]第四军医大学西京医院眼科、金军眼科研究所,陕西省西安市710032

出　　处：《眼科新进展》2010年第7期605-611,共7页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(编号:30500550);陕西省自然科学基金资助(编号:2006C226)~~

摘　　要：目的探讨贝伐单抗(Avastin)滴眼液对兔眼碱烧伤或缝线诱导角膜新生血管的抑制作用。方法 54只家兔分别以碱烧伤法(27只)和缝线法(27只)诱导角膜新生血管模型,根据治疗方法不同随机再分为3组:Avastin眼液组、复方硫酸新霉素眼液组和生理盐水组。各组均于诱导后第7天给予相应药物滴眼,4次.d-1,共14d。造模后第7天、第21天、第28天、第56天计算角膜新生血管面积,免疫组织化学法检测角膜组织中VEGF蛋白表达,RT-PCR法检测角膜组织中VEGFmRNA表达,酶联免疫吸附测定法(ELISA)检测房水内VEGF蛋白表达。结果碱烧伤后第21天、第28天、第56天Avastin眼液组和复方硫酸新霉素眼液组角膜新生血管面积明显较生理盐水组短而稀疏,其中3个不同时间点Avastin眼液组的角膜新生血管面积分别为(26.16±7.02)mm2、(29.71±10.43)mm2、(26.10±10.72)mm2,均明显小于生理盐水组,差异均有统计学意义(均为P<0.01);缝线后第21天、第28天、第56天时Avastin眼液组新生血管面积分别为(18.26±3.88)mm2、(37.24±3.16)mm2、(40.16±3.38)mm2,均明显小于复方硫酸新霉素眼液组和生理盐水组,差异均有统计学意义(均为P<0.01);碱烧伤或缝线诱导后第21天,免疫组织化学结果显示Avastin眼液组角膜上皮层VEGF蛋白表达较生理盐水组均减弱,基质层新生血管较少;RT-PCR显示造模后第21天和第28天时,Avastin眼液组兔角膜组织内VEGFmRNA的表达均明显低于生理盐水组,差异均有统计学意义(均为P<0.01),而造模后第56天时,Avastin眼液组和复方硫酸新霉素眼液组VEGFmRNA的表达均较生理盐水组高,差异均有统计学意义(均为P<0.05);ELISA结果显示Avastin眼液组在碱烧伤和缝线诱导后第21天,房水VEGF蛋白含量分别为(81.0±8.7)ng.L-1、(110.0±9.0)ng.L-1,均明显低于复方硫酸新霉素眼液组和生理盐水组,差异均有统计学意义(均为P<0.01)。结论 Avastin滴眼液能有效地抑制兔眼�Objective To investigate the effect of bevacizumab （Avastin） eye drops on inhibiting corneal neovascularization （CNV） induced by corneal alkali burn or suture in rabbits.Methods CNV was induced by alkali burn or suture in 27 rabbits respectively.Then the two groups were divided into Avastin eye drops,steroid eye drops,PBS control groups according to the treatments.Seven days after the alkali burn or suture injury,rabbits of each group received respective treatments,4 times a day for 14 days.On the 21st day,28th day,and 56th day after the injury,the area of CNV was examined;VEGF protein and mRNA expression in corneal tissues,VEGF protein expression in aqueous were detected by immunohistochemistry,RT-PCR and enzyme-linked immunosorbent assay （ELISA） respectively.Results CNV was significantly shorter and sparser in Avastin eye drops group and steroid eye drops group than that in PBS control group on the 21st day,28th day,and 56th day after the alkali burn.At three different time points,in Avastin eye drops group the area of CNV were （26.16±7.02） mm2,（29.71±10.43） mm2 and （26.10±10.72） mm2 respectively,which were significantly lower than that in PBS control group,there were all significant differences（all P0.01）.On the 21st day,28th day,and 56th day after the suture injury,the area of CNV in Avastin eye drops group was （18.26±3.88） mm2,（37.24±3.16） mm2 and （40.16±3.38） mm2 respectively,which were significantly less than that in steroid eye drops group and PBS control group,there were all significant differences（all P0.01）.In both models,VEGF protein expression in corneal epithelium in Avastin eye drops group more decreased markedly than that in PBS control group,with less neovascularization in stroma by immunohistochemistry on the 21st day after the alkali burn or suture injury.Results of RT-PCR showed that the expression of VEGF mRNA in corneal tissues in Avastin eye drops group was significantly lower than that in PBS control group on the 21st,28th day in both model

关 键 词：贝伐单抗 角膜新生血管 血管内皮生长因子 兔 

分 类 号：R772.2[医药卫生—眼科] Q959.836[医药卫生—临床医学]