4  血管生长因子与糖尿病视网膜病变

　　目前发现的血管生长因子很多，其中血管内皮生长因子（VEGF）表达增加已经成为目前糖尿病视网膜病变发病机制的研究焦点。VEGF是血管系统形成的必需成分。目标性破坏（敲除）大鼠VEGF基因，可导致血管形成障碍和子宫内死亡。组织缺氧可增强VEGF的表达，而这正是视网膜新生血管形成的一个主要刺激物。甚至在可识别视网膜病变早期征象如毛细血管周细胞和内皮细胞消失之前，就已经存在视网膜血流减少和伴发组织缺氧，并且这些变化很可能伴有VEGF合成及分泌的增加［4］。研究发现有糖尿病倾向的大鼠在糖尿病尚未确诊前，视网膜上VEGF表达即有轻度增加；当糖尿病发作后，视网膜上VEGF、VEGF mRNA和VEGF受体表达都明显增加［22］。视网膜神经节细胞层及内、外核层VEGF及其受体 flk-1及 flt-1表达也显著增高［23］。Juan等发现6周的糖尿病大鼠视网膜VEGF及其受体flk-1、bFGF（成纤维细胞生长因子）和有丝分裂原激活蛋白激酶（MAPK）和酪氨酸激酶(TK)表达增加。异黄酮的治疗可抑制糖尿病大鼠视网膜上的TK蛋白质的磷酸化表达，而对VEGF、flk-1和bFGF无影响［24］。

　　在糖尿病鼠的视网膜上发现IGF-I（胰岛素样生长因子）受体和Akt磷酸化水平轻度增高。色素上皮细胞上IGF-1基因的高表达,能使色素上皮细胞趋化迁移及增生，这可能与糖尿病视网膜病变的增殖性病变有关［25］。

　　5  小结

　　糖尿病视网膜病变动物模型是在糖尿病模型基础上发展而来的。多数的动物模型仅表现为背景性糖尿病视网膜病变，增殖性视网膜病变少见。常用的糖尿病视网膜病变实验动物有猴、猫、狗、猪、鼠等。利用糖尿病视网膜病动物模型实验，可以从不同角度对疾病的发病机制和治疗进行研究。

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