FLK-1单克隆抗体抑制实验性视网膜血管新生的实验研究

目的:观察血管内皮生长因子受体2(FLK-1)单克隆抗体(anti-FLK1mAb)对视网膜新生血管形成(retinal neovascularization,RNV)的抑制作用,同时分析其对缺血性视网膜病变的影响。方法:将生后第7d的C57BL/6幼鼠置于高氧箱中饲养5d后取回至正常空气环境诱导RNV模型,生后第12,13,15d利用腹腔注射的方法给与实验组小鼠anti-FLK1 mAb500μg(对照组给与等量的大鼠免疫球蛋白),生后第17d处死动物行视网膜铺片和免疫组织化学染色检查,测量视网膜血管无灌注区的面积,计数RNV内皮细胞核数目,定量分析anti-FLK1 mAb对于缺血性视网膜病变以及实验性RNV形成的影响。结果:对照组和实验组均成功建立了RNV模型,实验组RNV的形成明显受到抑制(P<0.01),同时anti-FLK1 mAb也加重了RNV模型的缺血过程(P<0.05)。结论:拮抗FLK-1可以有效抑制RNV的形成,提示拮抗FLK-1可能成为治疗RNV有效的生物学方法之一,其可能加重缺血性视网膜病变的潜在副作用需进一步探讨。

Suppression of anti-FLK1 monoclonal antibody to experimental retinal neovascularization

AIM: To investigate the effects of neutralizing FLK-1 on retinal neovascularization (RNV) and ischemic retino-pathy in the mouse model of oxygen-induced retinopathy (OIR).·METHODS: C57BL/6 mice at postnatal day (P) 7 were exposed to 750mL/L oxygen for 5 days (until P12) and allowed to recover in room air to induce RNV. At P12, P13 and P15, the animals were intraperitoneally injected with anti-FLK1 monoclonal antibody 500μg. Control mice were injected with rat IgG at same dose. Retinal fluorescein angiography and immunohistochemical staining were used to assess the development of ischemic retinopathy and experimental RNV quantitatively at P17, by measuring the area of vascular obliteration and counting the number of preretinal nuclei.·RESULTS: Anti-FLK1 significantly inhibited formation of RNV (P<0.01) and revascularization of the ischemic retina (P<0.05) compared with those of control mice. ·CONCLUSION: Our findings suggest that FLK-1 may be a promising potential target for antiangiogenesis therapy for RNV. Further research is needed to decrease the undesirable effect of inhibiting retinal revascula-rization.·