目的：探讨越橘提取物对视网膜色素上皮(retinal pigment epithelial,RPE)细胞氧化损伤和血管生成的抑制作用。方法：① 将人RPE细胞(ARPE-19)分为对照组、模型组、越橘提取物组，模型组给予0.5 mmol/L3-吗啉代亚胺 (3 morpholinosydnonimine,SIN-1)处理24 h，越橘提取物组给予10ng/mL越橘提取物处理1h 后，再给予0.5 mmol/L SIN-1处理24 h。细胞活性检测法(Cell Counting Kit-8,CCK-8)测定各组细胞活性，流式细胞术检测细胞活性氧(reactive oxygen species,ROS)水平。②将人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)分为对照组、模型组、越橘提取物组，模型组给予10 ng/mLVEGF处理8 h，越橘提取物组给予10 ng/mL越橘提取物处理12 h后，再给予10 ng/mLVEGF处理8 h。划痕实验和Transwell实验检测细胞迁移和侵袭，管腔形成实验检测细胞血管生成情况。结果：①越橘提取物在质量浓度≤10 ng/mL对 ARPE-19细胞无明显毒性。给予SIN-1处理后，ARPE-19细胞活性明显降低，而预孵10 ng/mL越橘提取物

可使细胞活性恢复接近至正常(P<0.001)，后续实验均选用该浓度。同时，越橘提取物可降低SIN-1诱导的ARPE-19细胞内ROS水平(P<0.0001)。②给予VEGF处理后，HUVEC细胞迁移和侵袭能力增强，而预孵越橘提取物可使细胞迁移和侵袭能力减弱(P<0.0010)。同时，越橘提取物可抑制VEGF诱导的HUVEC细胞小管形成(P<0.0001)。结论：越橘提取物具有较强的抗氧化能力和抗血管生成活性，为其作为潜在治疗年龄相关性黄斑变性治疗药物提供了科学依据。

Objective: To investigate the inhibitory effects of bilberry extract on oxidative damage and angiogenesis in retinal pigment epithelial (RPE) cells. Methods:  Human RPE cells (ARPE-19) were divided into control, model and bilberry extract groups. The model group was treated with 0.5 mmol/L SIN-1 for 24 h, and the bilberry extract group was treated with 10ng/bilberry extract for 1 hour, followed by 0.5mmol/L SIN-1 for 24 h. Cell viability was measured by CCK-8. Level of reactive oxygen species (ROS) was determined using flow cytometry. Human umbilical vein endothelial cells (HUVEC) were divided into three groups, control group, model group and bilberry extract group. The model group was treated with 10ng/mL VEGF for 8 h, and the bilberry extract group was treated with 10 ng/mL bilberry extract for 12 h, followed by 10ng/mLVEGF for 8 h. Cell migration and invasion were measured by wound healing assay and Transwell assay. Cell angiogenesis was determined by tube formation assay. Results: 1. Bilberry extract had no obvious toxicity to ARPE-19 cells(≤10 ng/mL). AfterSIN-1 treatment , the the viability of ARPE-19 cells was significantly reduced, while incubation with 10 ng/ml bilberry extract could restore cell activity to the normal levels(P<0.001). This concentration was selected for subsequent experiments. Additionally, bilberry extract reduced the level of ROS in SIN-1-induced ARPE-19 cells(P<0.0001). VEGF treatment significantly enhanced the migration and invasion of HUVEC, whil epretreatment with bilberry extract attenuated these effects(P<0.0010). Meanwhile, bilberry extract could significantly inhibit VEGF-induced tube formation in HUVEC(P<0.0001). Conclusion: Bilbery extract possess strongantioxidant and anti-angiogenetic activities, suggesting its potential as treatment agent for AMD.