| 冯亚辉,蒋胜,涂文玲,等.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[J].中华放射医学与防护杂志,2021,41(8):602-608.Feng Yahui,Jiang Sheng,Tu Wenling,et al.Effect of ionizing radiation on ferroptosis of skin cells and the radioprotective role of ferroptosis inhibitor Ferrostatin-1[J].Chin J Radiol Med Prot,2021,41(8):602-608 |
| 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 |
| Effect of ionizing radiation on ferroptosis of skin cells and the radioprotective role of ferroptosis inhibitor Ferrostatin-1 |
| 投稿时间：2020-12-04 |
| DOI：10.3760/cma.j.issn.0254-5098.2021.08.007 |
| 中文关键词: 电离辐射 皮肤 铁死亡 Ferrostatin-1 辐射防护 |
| 英文关键词:Ionizing radiation Skin Ferroptosis Ferrostatin-1 Radioprotection |
| 基金项目:国家自然科学基金（82073477，32071238） |
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| 中文摘要: |
| 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）释放检测X射线照射以及Fer-1处理对HaCaT细胞存活和细胞死亡的影响。采用流式细胞术检测X射线照射以及Fer-1处理后对HaCaT细胞脂质过氧化水平的影响。利用结晶紫染色法检测X射线照射以及Fer-1处理对HaCaT细胞克隆形成能力的影响。Western blot检测X射线照射以及Fer-1处理对铁死亡相关蛋白ACSL4和GPX4表达的影响。结果 单纯照射组经不同剂量的X射线照射后细胞存活率明显降低（t=5.63、8.74，P<0.05），LDH的释放明显增加（t=3.98、5.08、9.27，P<0.05），Fer-1能够提高受照射皮肤细胞存活率（t=5.79，P<0.05），降低LDH的释放量（t=12.36、11.96、18.13、9.96，P<0.05）。单纯照射组经10 Gy的X射线照射后细胞的脂质过氧化水平明显升高（t=9.59，P<0.05），克隆存活能力明显减弱（t=4.26，P<0.05），而Fer-1能够降低X射线照射引起的脂质过氧化水平的升高（t=6.48、17.04，P<0.05），增加受照射皮肤细胞的克隆存活能力（t=3.96，P<0.05）。10 Gy的X射线照射会导致ACSL4表达水平的升高和GPX4的表达水平的降低，而Fer-1的治疗能促进ACSL4和GPX4的表达水平恢复正常（t=5.23、7.16、4.78、8.29、6.43，P<0.05）。结论 铁死亡抑制剂Fer-1在细胞水平上能够通过抑制电离辐射后铁死亡的发生而保护皮肤细胞，为放射性皮肤损伤的防护提供了一种新的策略。 |
| 英文摘要: |
| 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. |
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