电离辐射对皮肤细胞铁死亡的影响及其抑制剂Ferrostatin-1的防护作用研究

目的:探讨电离辐射对皮肤细胞铁死亡的影响以及铁死亡抑制剂Ferrostatin-1(Fer-1)对受照射皮肤细胞的保护作用及机制。方法:为检测Fer-1对人永生化角质形成细胞(HaCaT)辐照后的影响，按照射与给药方式分为对照组、Fer-1组、单纯照射组、照射+Fer-1组。采用CCK-8法和乳酸脱氢酶(LDH)释放检...

Effect of ionizing radiation on ferroptosis of skin cells and the radioprotective role of ferroptosis inhibitor Ferrostatin-1

Objective To investigate the effect of ionizing radiation on the ferroptosis of skin cells and the potential therapeutic strategy of ferroptosis inhibitor Ferrostatin-1 (Fer-1) on irradiated skin cells.Methods HaCaT cells were pre-treated with Fer-1 before X-ray irradiation. After irradiation, CCK-8 assay and LDH release assay were used to detect cell viability and cell death, flow cytometry was used to detect the lipid peroxidation levels, crystal violet staining assay was used to detect colony forming ability, and the expressions of ferroptosis related proteins ACSL4 and GPX4 were detected by Western blot.Results The cell viability of HaCaT cells was significantly decreased (t=5.63, 8.74, P<0.05) and the release of LDH was significantly increased (t=3.98, 5.08, 9.27, P<0.05) after different doses of X-ray irradiation. The cell viability was improved (t=5.79, P<0.05) and the release of LDH was reduced (t=12.36, 11.96, 18.13, 9.96, P<0.05) after the pre-treatment with Fer-1. The lipid peroxidation levels of HaCaT cells were significantly increased (t=9.59, P<0.05) and the clonogenic survival ability were reduced (t=4.26, P<0.05) after 10 Gy X-ray irradiation, while Fer-1 pre-treatment reduced (t=6.48, 17.04, P<0.05) the increase of lipid peroxidation level induced by X-ray irradiation and also effectively restore (t=3.96, P<0.05) the clonogenic survival ability. The expressions of ACSL4 and GPX4 were decreased after 10 Gy X-ray irradiation, while they recovered to normal level (t=5.23, 7.16, 4.78, 8.29, 6.43, P<0.05) after the pre-treatment with Fer-1.Conclusions Ferroptosis inhibitor Fer-1 alleviates the progress of radiation-induced skin injury by inhibiting ferroptosis after ionizing radiation at the cellular level, which provides a potential strategy for the protection of radiation injury.