As_2O_3对兔角膜碱烧伤后HIF-1及iNOS表达的影响

Effection of As_2O_3 on expression of HIF-1 and iNOS following corneal alkali burns in the rabbit

目的通过研究兔角膜碱烧伤后不同时期缺氧诱导因子-1(HIF-1)、诱导性一氧化碳合成酶(iNOS)及血管内皮生长因子(VEGF)在角膜的表达,观察局部应用三氧化二砷(As2O3)对兔角膜碱烧伤后HIF-1、iNOS及VEGF表达的影响,探讨HIF-1及iNOS在As2O3抑制角膜新生血管形成中的作用机制。方法日本大耳白兔48只,碱烧伤法建立兔角膜新生血管动物模型,随机分成A、B、C、D四组,实验组(A、B、C组)分别给予不同剂量的三氧化二砷结膜下注射,对照组(D组)给予生理盐水结膜下注射,观察角膜新生血管的生长情况,免疫组化法检测烧伤后第7、14、28天角膜组织中HIF-1、iNOS及VEGF的表达。结果兔角膜碱烧伤后,实验组角膜新生血管的面积小于对照组(P<0.05),且随As2O3剂量的增加而减少;免疫组化法显示实验组角膜组织中HIF-1、iNOS及VEGF的表达水平低于对照组(P<0.05)。结论 As2O3对兔角膜碱烧伤后角膜新生血管的形成具有抑制作用;HIF-1和iNOS是重要的角膜新生血管形成因子,As2O3抑制角膜新生血管形成的机制可能是与HIF-1和iNOS的表达有关。

Objective To observe the expression of HIF-1 and iNOS and VEGF following alkali burus in the rabbit cornea and find out the effection of As2O3 on expression of HI-land iNOS and VEGF. To study the mechanism of HIF-1 and iNOS inhibition of As2O3 on the cornea neovascularization. Methods To induce the models of alkai bums in Japanese rabits. Rabbits were randomly divided into 4 groups. Different concentration of As2O3 were used in the experimental group with subconjunctival injection. And the control group was subconjunctival injection with 0. 3ml 0. 9% of normal saline. CNV was observed everyday with slit lamp microscope after alkali burns 24 hours. To detected the expression of HIF-1 and iNOS and VEGF by immunohistechemical techniq. Results The neovascularization area of cornea and the expression of HIF-1 and iNOS and VEGF after alkali burn with As2O3 were less than those of contrast （ P 〈 0.05 ） ; The difference was significant with the increasing of the dose of As2O3. Conclusion As2O3 can inhibit the cornea neovascularization after cor- neal bums; HIF-1 and iNOS are important angiogenic factors in the process of forming corneal neovascularization;The mechanism of As2O3 inhibiting corneal neovascularization is probably associated with the inhibitive expression of HIF-1 and iNOS.