方法：将新生C57BL/6J小鼠随机分为3组，分别为正常对照组、VAS2870注射OIR组和无菌PBS缓冲液注射OIR组。将后两组小鼠在出生后第7d(P7)至P12置于体积分数为75%±2%的恒定高氧氧箱中以构建OIR模型，在P12时给予幼鼠双眼玻璃体腔注射VAS2870(0.5μL)，另一组幼鼠双眼注射同等剂量的无菌PBS缓冲液。三组小鼠均在P17时取右眼行视网膜铺片和Lectin染色，观察视网膜中央无血管区及病理性新生血管的情况； 取右眼行视网膜组织定量检测ROS/RNS含量； 取左眼应用RT-PCR检测Nox4 mRNA含量，并应用Western-blot测定视网膜组织中VEGF的表达。

结果：VAS2870注射OIR组小鼠视网膜中央无血管区面积较无菌PBS缓冲液注射OIR组明显减少(P<0.05)，病理性新生血管数目明显减少(P<0.05)； VAS2870注射OIR组小鼠视网膜组织Nox4 mRNA的表达量明显低于无菌PBS缓冲液注射组； VAS2870注射OIR组小鼠视网膜组织ROS含量较无菌PBS缓冲液注射组明显降低(P<0.05)； VAS2870注射OIR组小鼠视网膜组织VEGF的表达明显低于无菌PBS缓冲液注射组(P<0.05)。

结论：在小鼠OIR模型中，VAS2870可抑制Nox4 mRNA的表达，减少ROS/RNS，下调VEGF的生成，在视网膜病变进程中具有保护作用。

METHODS: Neonatal C57BL/6J mice were divided randomly into three groups: normoxic control group, PBS injection of OIR group and VAS2870 injection of OIR group. The mice of the latter two groups were exposed to 75% oxygen from the postnatal 7d(P7)to the postnatal 12d(P12)to induced OIR. VAS2870 was administered by intravitreal injection(0.5μL)in a mice model of OIR in P12. Another set of mice model of OIR were received a similar treatment with PBS. All eyes were collected at P17. The right eyes were whole mounted and stained with Lectin to observe the growth of retinal vessels; The eyes were enucleated to assess the levels of reactive oxygen species ROS/RNS. The expression of vascular endothelial growth factor(VEGF)and Nox4 mRNA were detected by western blot and RT-PCR, respectively.

RESULTS: In the retina of OIR, VAS2870 reduced the retinal avascular area and neovascularization, the hypoxia-induced increase in ROS levels, the protein expression of VEGF and gene expression of Nox4 mRNA.

CONCLUSION: NOX4 enzyme inhibition with VAS2870 has potent anti-oxidative stress effects in the retina, indicating its potential as a treatment for retinopathy of prematurity.