RXRα激动剂贝沙罗汀通过缓解氧化应激减轻辐射引起的皮肤损伤

Q1 Health Professions Radiation Medicine and Protection Pub Date : 2022-06-01 DOI:10.1016/j.radmp.2022.04.004

Sheng Jiang , Weichao Cai , Jianhui Chen , Wenling Tu , Yulan Liu , Lixin Gong , Yahui Feng , Wei Mo , Tao Yan , Shuyu Zhang , Daojiang Yu

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摘要

目的探讨贝沙罗汀对放射性皮肤损伤的保护作用，并探讨其机制。方法用x射线直线加速器建立辐射细胞模型和动物模型。CCK8和流式细胞术检测细胞活力和凋亡情况。贝沙罗汀对SD大鼠的体内保护作用进行了测定。用DCF-DA法验证了贝沙罗汀的抗氧化能力。通过RNA测序富集了贝沙罗汀介导的皮肤修复的信号通路。结果贝沙罗汀能明显恢复辐射损伤的WS1细胞的增殖并抑制其凋亡(P <0.05)。贝沙罗汀能有效缩短辐射性皮肤损伤大鼠模型的皮肤损伤过程，促进皮肤修复(P <0.05)。在机制上，贝沙罗汀可有效降低RXRα的表达(P <0.05)，从而导致辐射暴露后活性氧(ROS)的早期减少。此外，转录组分析表明，贝沙罗汀介导的辐射损伤恢复涉及氧化还原信号、免疫调节、脂质代谢和自噬。结论贝沙罗汀是治疗放射性皮肤损伤的理想药物。

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RXRα agonist bexarotene attenuates radiation-induced skin injury by relieving oxidative stress

Objective

To investigate the protective effect of bexarotene in radiation-induced skin injury and elucidate underlying mechanism.

Methods

Irradiated cellular and animal models were established using an X-ray linear accelerator. Cell viability and apoptosis were evaluated by CCK8 and flow cytometry. In vivo protective effect of bexarotene was measured in irradiated SD rats. The antioxidant capacity of bexarotene was validated by DCF-DA method. The signaling pathways involved in bexarotene-mediated skin repair were enriched by RNA sequencing.

Results

Bexarotene could significantly restore the proliferation and inhibit the apoptosis of WS1 cells with radiation damage (P < 0.05). Moreover, bexarotene could effectively shorten the process of skin damage and promote skin repair in a rat model of radiation-induced skin injury (P < 0.05). Mechanistically, bexarotene effectively reduced the expression of RXRα (P < 0.05), thus leading to an early decrease in reactive oxygen species (ROS) after radiation exposure. Furthermore, a transcriptome analysis indicated that bexarotene-mediated recovery of radiation damage involves redox signaling, immune regulation, lipid metabolism and autophagy.