| 江枫荻,刘一帆,欧小兰,等.非诺贝特对紫外线B诱导的皮肤损伤的保护作用及机制研究[J].中华放射医学与防护杂志,2026,46(7):641-649.Jiang Fengdi,Liu Yifan,Ou Xiaolan,et al.Study on the protective effects of fenofibrate against UVB-induced skin damage and its mechanisms[J].Chin J Radiol Med Prot,2026,46(7):641-649 |
| 非诺贝特对紫外线B诱导的皮肤损伤的保护作用及机制研究 |
| Study on the protective effects of fenofibrate against UVB-induced skin damage and its mechanisms |
| 投稿时间：2025-08-12 |
| DOI：10.3760/cma.j.cn112271-20250812-00293 |
| 中文关键词: 紫外线B 非诺贝特 过氧化物酶体增殖物激活受体α(PPARα) 光损伤 脂质组学 |
| 英文关键词:Ultraviolet B Fenofibrate Peroxisome proliferator-activated receptor α Photodamage Lipidomics |
| 基金项目:西藏自治区科技计划项目重点研发计划(XZ202501ZY0131);天府锦城实验室(前沿医学中心)成果转化项目(2025ZH006);四川省区域创新合作项目(2026YFHZ0164) |
| 作者 | 单位 | E-mail | | 江枫荻 | 四川大学华西基础医学与法医学院放射医学研究室, 成都 610041 | | | 刘一帆 | 四川大学华西基础医学与法医学院放射医学研究室, 成都 610041
天府锦城实验室(前沿医学中心), 成都 610093 | | | 欧小兰 | 核工业四一六医院整形烧伤科, 成都 610051 | | | 国林芬 | 四川大学华西医院烧伤整形外科, 成都 610041 | | | 王佳佳 | 西藏大学医学院, 拉萨 850000 | | | 熊海 | 西藏大学医学院, 拉萨 850000 | | | 余道江 | 核工业四一六医院整形烧伤科, 成都 610051 | | | 张舒羽 | 四川大学华西基础医学与法医学院放射医学研究室, 成都 610041
天府锦城实验室(前沿医学中心), 成都 610093 | zhang.shuyu@hotmail.com |
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| 中文摘要: |
| 目的 探讨过氧化物酶体增殖物激活受体α(PPARα)激动剂非诺贝特(fenofibrate)对紫外线B(UVB)诱导的皮肤损伤的影响及其潜在分子机制。方法 25只6~8周龄C57BL/6J野生型雄性小鼠,通过单次2 J/cm2 UVB照射构建皮肤损伤模型,将小鼠按完全随机法分为空白对照组、溶剂对照组、非诺贝特组、沙罗格列扎组及GW6471组,每组5只。照后立即皮下注射对应试剂,采用皮肤损伤评分和伤口面积测量评估照射后0~36 d的皮肤损伤情况;另取同品系小鼠分为空白对照组、UVB照射组、UVB+二甲基亚砜(DMSO)组及UVB+非诺贝特组,照射后第4天采集皮肤组织进行液相色谱-串联质谱脂质代谢组检测。在人成熟脂肪细胞中,分别加入DMSO、非诺贝特、沙罗格列扎或GW6471;在人永生化角质形成细胞(HaCaT细胞)中分别加入上述药物或对应培养基,采用流式细胞术检测UVB照射后细胞凋亡率,采用克隆形成实验检测细胞增殖能力,采用细胞划痕实验检测细胞迁移能力。结果 照后第36天与空白对照组小鼠相比,非诺贝特组小鼠在UVB照射后的皮肤损伤评分降低(t=5.17,P<0.05);照射5 mJ/cm2 UVB后,与DMSO组HaCaT细胞凋亡率(42.15±0.52)%相比,非诺贝特组凋亡率降低为(34.56±0.50)%(t=22.42,P<0.05);与DMSO组的克隆形成率(10.50±0.54)%相比,非诺贝特组的克隆形成率升高为(23.35±1.07)%(t=14.30,P<0.05);与空白对照组细胞迁移率(23.51±1.02)%相比,非诺贝特组24 h后的细胞迁移率升高为(28.46±1.28)%(t=22.84,P<0.05)。脂质组学分析显示,非诺贝特显著改变了UVB照射后皮肤中的多种脂质,包括OAHFA(40∶6)、PA(34∶4e)、TG(16∶0e/16∶0/22∶6)等脂质上调,TG(14∶0/18∶2/22∶6)、PG(28∶0/16∶0)、Cer(d17∶0/24∶0)等脂质下调。结论 非诺贝特可通过减轻皮肤损伤、促进伤口愈合、增强细胞抗凋亡能力及调节皮肤脂质代谢紊乱等多种机制显著缓解UVB照射诱导的皮肤损伤。 |
| 英文摘要: |
| Objective To investigate the effects of the peroxisome proliferator-activated receptor α agonist fenofibrate on ultraviolet B (UVB)-induced skin damage and its underlying molecular mechanisms. Methods Twenty-five male C57BL/6J wild-type mice aged 6-8 weeks, a skin damage model was established by a single 2 J/cm2 UVB irradiation. The mice were randomly divided into a blank control group, a vehicle control group, a fenofibrate group, a saroglitazar group, and a GW6471 group, with 5 mice in each group. The corresponding agents were injected subcutaneously immediately after irradiation, and skin damage scores and wound area measurements were used to evaluate skin damage from 0 to 36 d post-irradiation. In addition, mice of the same strain were divided into a negative control group, a UVB irradiation group, a UVB+DMSO group, and a UVB+fenofibrate group. Skin tissue was collected at 4 d post-irradiation for lipid metabolomics analysis using liquid chromatography-tandem mass spectrometry. Human mature adipocytes were treated with DMSO, fenofibrate, saroglitazar, or GW6471 for 24 h, the culture medium was replaced with fresh medium, the incubation was continued for another 24 h, and the adipocyte-conditioned medium was collected. The above drugs or corresponding conditioned media were added to human immortalized keratinocytes (HaCaT cells), respectively. Flow cytometry was used to determine the apoptosis rate after UVB irradiation, the colony formation assay was used to assess the cell proliferation ability, and the cell scratch assay was used to evaluate the cell migration ability. Results Compared with the control group, the skin damage score of mice in the fenofibrate group decreased after UVB irradiation at 36 d (t=5.17, P<0.05). Compared with the apoptosis rate of (42.15±0.52)% in the DMSO group irradiated with 5 mJ/cm2 UVB, the apoptosis rate of HaCaT cells in the fenofibrate group irradiated with 5 mJ/cm2 UVB decreased to (34.56±0.50)% (t=22.42, P<0.05). Compared with the colony formation rate of (10.50±0.54)% in the DMSO group irradiated with 5 mJ/cm2 UVB, the colony formation rate of HaCaT cells in the fenofibrate group irradiated with 5 mJ/cm2 UVB increased to (23.35±1.07)% (t=14.30, P<0.05). Compared with the cell migration rate of (23.51±1.02)% in the Mock group, the cell migration rate in the fenofibrate group at 24 h increased to (28.46±1.28)% (t=22.84, P<0.05). Lipidomic profiling revealed that fenofibrate significantly altered various lipids in the skin after UVB irradiation, including the up-regulation of lipids such as OAHFA(40∶6), PA(34∶4e), and TG(16∶0e/16∶0/22∶6), and the down-regulation of TG(14∶0/18∶2/22∶6), PG(28∶0/16∶0), and Cer(d17∶0/24∶0). Conclusions Fenofibrate can significantly alleviate UVB-induced skin damage through multiple mechanisms, such as reducing skin damage, promoting wound healing, enhancing anti-apoptotic capacity of cells, and regulating disordered lipid metabolism in the skin. |
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