不同吸氧浓度对新生鼠视网膜血管发育和血管内皮生长因子表达的影响

Oxygen concentration variation influences the severity of retinopathy and vascular endothelial growth factor expression in newborn rats

背景:吸氧在早产儿视网膜新生血管中起重要作用,但其具体吸氧范围以及作用机制仍不明确。目的:观察不同氧环境在新生鼠视网膜病的作用。方法:将新生鼠40只分为空气组、波动1,2,3组,各10只,分别以正常空气、浓度50%、20%变化氧气、40%、10%变化氧气、50%、10%变化氧气环境饲养。饲养14d后,视网膜铺片经ADP酶染色和视网膜切片经常规苏木精-伊红染色观察视网膜血管的增生情况。Western blot检测视网膜血管内皮生长因子的表达。结果与结论:视网膜铺片波动2,3组新生血管钟点数、突破视网膜内界膜的血管内皮细胞数和血管内皮生长因子表达水平明显高于空气组和波动1组,空气组和波动组1组未见明显的视网膜新生血管。证实了反复血氧浓度波动可导致新生鼠视网膜新生血管增生性病变,吸入氧浓度差的波动与病变程度有关;低氧比高氧对发生视网膜病变可能更重要,血管内皮生长因子在视网膜新生血管形成中起着重要作用,促进视网膜新生血管形成。

BACKGROUND：Oxygen plays an important role in premature retinal neovascularization,but its scope of oxygen and the specific mechanism of retinopathy are not clear.OBJECTIVE：To study the effects of different concentrations of oxygen on neovascularization in oxygen-induced retinopathy of newborn rats.METHODS：Forty newly born rats were divided into four groups：air group（10 rats） was raised in air room.Fluctuation group 1,2,3（10 rats） was exposed to cycles of 50%-20%,40%-10%,50%-10% for 14 days,respectively.Retinas were dissected and stained by adenosine-diphosphatase（ADPase） histochemistry for assessment of intraretinal vascular development and preretinal angiogenic vessel growth.Expressions of vascular endothelial growth factor（VEGF） were studied by Western-blot.RESULTS AND CONCLUSION：Retina flat-mounts presented increasing neovascular tufts,severity of retinal neovascularization and the number of vascular nuclei extending from the internal limiting membrane into the vitreous,as well as VEGF-expression in fluctuation group 2 and fluctuation group 3.There were no obviously neovascularization in the air and fluctuation 1 groups.This study suggested that a small change in blood oxygen profile could trigger a disproportionate increase in subsequent neovascularization,accompanied by changes of retinal VEGF level.VEGF promote retinal neovascularization.The over-expression of VEGF plays a synergistic role during the formation of neovascularization.Partial pressure of inspiratory oxygen was positively correlated with the retinopathy.Hypoxia may be more important for retinal neovascularization on the occurrence of retinopathy than hyperoxia.