Avastin对兔虹膜新生血管形成、VEGF和TGF-β_2表达的影响  

Effects of Avastin on the formation of iris neovascularization,VEGF and TGF-β_2 expression in rabbits

作　　者：刘家苏 王茜[1] 刘升强[1] 李静敏[1] LIU Jiasu;WANG Qian;LIU Shengqiang;LI Jingmin(Ophthalmology Department,the Second Affiliated Hospital of Dalian Medical University,Dalian 116027,China)

机构地区：[1]大连医科大学附属第二医院眼科,辽宁大连116027

出　　处：《大连医科大学学报》2019年第2期102-106,共5页Journal of Dalian Medical University

摘　　要：目的研究Avastin对兔眼虹膜新生血管形成(NVI)、血管内皮生长因子(VEGF)及转化生长因子-β_2(TGF-β_2)的影响,明确Avastin对NVI的治疗作用。方法对14只雄性新西兰大白兔双眼行上、下直肌离断合并4条涡静脉阻塞手术,建立兔眼NVI模型。14只新西兰大白兔按照随机数字表法分为实验组和对照组,每组7只。于术后第5天实验组大白兔双眼均行玻璃体腔内注射Avastin 0.05 mL(含Avastin 1.25 mg),对照组大白兔双眼均行玻璃体腔内注射生理盐水0.05 mL。于术前1天及术后第1天、3天、5天、7天、9天、11天应用裂隙灯观察眼前节炎症反应及新生血管情况,比较房水血管内皮生长因子(VEGF)、TGF-β_2水平。术后第11天处死兔子,取眼球部分前节组织,应用HE染色观察并计数NVI数目,应用免疫组化测定VEGF和TGF-β_2表达量。结果实验组玻璃体内注射Avastin后NVI开始消退,此后新生血管数量继续减少,而对照组NVI则随造模时间延长而增多,并于术后第9天达到高峰,术后第11天实验组虹膜组织切片上NVI数量少于对照组(P<0.05)。免疫组化显示,对照组虹膜基质层及前缘层可见VEGF和TGF-β_2明显阳性表达,实验组虹膜基质层及前缘层可见VEGF和TGF-β_2微量散在阳性表达,实验组VEGF和TGF-β_2在蛋白水平的表达量明显低于对照组(P<0.05)。实验组在玻璃体腔内注射Avastin后,VEGF和TGF-β_2两种因子在房水中表达即开始降低,此后二者的表达量逐渐降低,术后7天、9天、11天实验组房水中VEGF及TGF-β_2表达明显低于同期对照组(P<0.05)。结论 Avastin可能能够通过抑制VEGF和TGF-β_2的表达,抑制NVI的形成和生长。Objective To study the effect of Avastin on iris neovascularization (NVI) and VEGF,transforming growth factor-β2 (TGF-β2) expression in rabbits in order to clarify its therapeutic effect.Methods NVI models of 14 male New Zealand white rabbits were established by bilateral superior and inferior rectus muscle amputation combined with 4 eddy veins occlusion.These rabbits were randomly and evenly divided into experimental group and control group.Avastin (25 mg/ mL) and saline was injected into the vitreous cavity of both eyes (0.05 mL each) in the experimental group and control group respectively.The inflammation and neovascularization of anterior segment were observed by slit lamp on the 1st day before operation and the 1st,3rd,5th,7th,9th and 11th day after operation.VEGF and TGF-β2 expression in aqueous humor were detected with ELISA.After rabbits were sacrificed on the 11th day of operation,the anterior segment of the eyeball was harvested.The number of NVI was observed and counted on the histological slides with HE stains.VEGF and TGF-β2 expression were measured with immunohistochemistry.Results NVI began to subside in the experimental group after intravitreal injection of Avastin,and the number of neovascularization continued to decrease.NVI in the control group increased with the prolongation of modeling time and reached a peak on the 9th day after operation.On the 11th day after operation,the number of NVI in the experimental group was less than that in the control group ( P <0.05).VEGF and TGF-β2 expression in the iris stroma and anterior layer was significantly weaker in the experimental group than those in the control group ( P <0.05).And those expression in aqueous humor of the experimental group was also significantly lower in the experimental group on the 7th,9th and 11th day after operation ( P <0.05).Conclusion Avastin would inhibit NVI and growth by inhibiting VEGF and TGF-β2 expression.

关 键 词：虹膜新生血管 血管内皮生长因子 转化生长因子-Β2 AVASTIN 

分 类 号：R737.33[医药卫生—肿瘤]