vegf和inos作为缺氧性视网膜病变干预靶点的实验研究眼科学专业论文.docxVIP

电镜观察视网膜上VEGF和iNOS表达的特征、视网膜新生血管形成以 电镜观察视网膜上VEGF和iNOS表达的特征、视网膜新生血管形成以 及组织形态结构的变化。 【结果】小鼠视网膜上VEGF和iNOS的mRNA和蛋白表达水平均上 调，并呈较为明显的时间依赖性特征，其中VEGF表达高峰在6h，iNOS 表达高峰在2h，均以视网膜的节细胞层表达变化明显。RB细胞中VEGF 和iNOS的mRNA和蛋白表达水平也均上调，里较为明显的时间依赖性 特征，表达特征与在动物模型中表达基本一致。在干预组中，VEGF在 Bevacizumab组表达水平明显上升，而在AG组和联合用药组表达水 平下降。iNOS表达水平在Bevacizumab组表达水平无明显改变，而 在AG组和联合用药组表达水平下降。Bevacizumab和氨基胍(AG) 可以明显抑制氧诱导的小鼠新生血管模型中新生血管的形成。三个干 预组中的血管内皮细胞数与Ns组和对照组相比具有显著统计学差异 (P(O．05)。在干预组中没有出现明显的组织学的结构改变。 【结论】VEGF和iNOS是缺氧性视网膜病变中血管生成的早期治 疗靶点。AG不仅可以抑制iNOS，而且对VEGF也有部分抑制作用， 且无明显的药物毒性，它抑制新生血管形成的效应至少与 Bevacizumab是等效的，因此AG可以作为抑制新生血管形成的药物。 关键词：缺氧，新生血管，血管内皮生长因子，诱导型一氧化氮合成 酶 THE THE STUDY OF VEGF AND iNoS AS RATIONAL INI’ERVENTIONAL TARGETS IN HYPOXIA．INDUCED ABSTRACT BACKGROUND AND AIMS：New blood vessel formation is one of the major pathological changes in the hypoxia retinopathy．A lot of angiogenic factors involved in this process．This study is to evaluate the role of vascular endothelial growth factor,VEGF,and inducible nitric oxide synthase，iNOS as rational interventional targets in hypoxia。induced retinopathy．Simultaneously,the compensative changes in the signal pathway within the signal transduction network after the inhibition of VEGF by its monoclonal antibody,Bevacizumab，and iNOS by its chemical compound inhibitor,aminoguanidine(AG)were evaluated． The impacts of Bevacizumab，AG as well as their combination regimen on retinal neovasculariation and the expression of VEGF and iNOS were determined． MATERIALS AND METHODS：RT-PCR，immunobistochemistry staining(IHC)and staining(IHC)and western blot assay were used tO detect the expression levels of retinal VEGF and iNOS mRNA and protein respectively in the early stage of oxygen-induced retinopathy in mouse model．RT-PCR and ‘western blot assay were used to determine the expression patterns of retinal VEGF and iNOS mRNA and protei日respectively in retinoblastoma under hypoxia conditions in the early stage．RT-PCR，IHC staining，retinal fluorescein angiography and electron microscop