目的：探讨蓝光诱导人视网膜色素上皮(ARPE)细胞铁死亡的发生及可能机制。

方法：体外培养的ARPE-19细胞接受405nm蓝光50mW/cm²辐照度照射不同时间，分为对照组、16.3J/cm²组、32.6J/cm²组和65.2J/cm²组； 将65.2J/cm²组定为高能量蓝光照射组，进一步分为对照组、高能量蓝光照射组和高能量蓝光照射+铁死亡抑制剂组，CCK-8检测细胞活力，试剂盒检测细胞内谷胱甘肽(GSH)含量、二价铁离子浓度及丙二醛(MDA)含量，Western blot法检测细胞内GPX4和xCT蛋白相对表达量。

结果：蓝光照射导致ARPE-19细胞活力下降呈剂量依赖性，高能量蓝光照射导致细胞内GSH含量下降，二价铁离子浓度和MDA含量上升(均P<0.05)； 加入铁死亡抑制剂可部分恢复蓝光照射组细胞活力和GSH含量，减少MDA含量，降低二价铁离子浓度(均P<0.05)； 蓝光照射组GPX4和xCT蛋白相对表达量显著下降，加入铁死亡抑制剂后蛋白表达量不同程度恢复(P<0.05)。

结论：蓝光照射可能通过影响xCT和GPX4相关抗氧化途径诱导RPE细胞铁死亡发生。

METHODS: ARPE-19 cells cultured in vitro were irradiated by 405 nm blue light at 50 mW/cm² irradiance with different duration and were divided into control, 16.3J/cm², 32.6J/cm², and 65.2J/cm² groups; the 65.2J/cm² group was defined as the high-level blue light irradiation group and cells were further divided into control, high-level blue light irradiation group and high-level blue light irradiation + ferroptosis inhibitor group. CCK-8 assay was used to detect cell viability, commercial kits were used to detect intracellular glutathione(GSH), ferrous iron and malondialdehyde(MDA)concentration, and Western blot was used to detect the relative expression of glutathione peroxidase 4(GPX4)and xCT proteins in cells.

RESULTS: The decrease of ARPE-19 cell viability caused by blue light irradiation was dose-dependent, and the reduction of intracellular GSH concentration, the increase of ferrous iron concentration and MDA concentration were all caused by high-level blue light irradiation(all P<0.05); the ferroptosis inhibitor partially restored cell viability and recovered intracellular GSH, reduced concentrations of MDA and ferrous iron in the blue light irradiation group(all P<0.05). The relative expressions of GPX4 and xCT proteins were significantly decreased in the blue light irradiation group, and such change was alleviated by the ferroptosis inhibitor(P<0.05).

CONCLUSION: Blue light irradiation may induce ferroptosis in RPE cells by targeting the xCT and GPX4-associated antioxidant pathways.