中华皮肤科杂志 ›› 2021, Vol. 54 ›› Issue (6): 469-474.doi: 10.35541/cjd.20201011

• 论著 • 上一篇    下一篇

白藜芦醇对苯并芘诱导的人皮脂腺细胞炎症因子及相关基因表达的影响

魏子妤1    侯霄枭1    曹珂1    李昕1    叶枫1    胡婷婷1    莫小辉1    陈广洁2    Christos C. Zouboulis3    鞠强1   

  1. 1上海交通大学医学院附属仁济医院皮肤科  200127；2上海交通大学医学院免疫学与微生物学系  200025；3Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodore Fontane, Dessau 06847, Germany
  • 收稿日期:2020-10-15 修回日期:2020-11-18 发布日期:2021-05-31
  • 通讯作者: 鞠强 E-mail:qiangju401@sina.com
  • 作者简介:2021年毕业急用，4月前
  • 基金资助:
    国家自然科学基金（81874247、81903234）；上海市科学技术委员会科研计划项目（19ZR1431300）；上海市卫生和计划生育委员会科研课题（20184Y0160）

Effects of resveratrol on expression of inflammatory cytokines and related genes in benzo（a）pyrene-induced human sebocytes

Wei Ziyu1, Hou Xiaoxiao1, Cao Ke1, Li Xin1, Ye Feng1, Hu Tingting1, Mo Xiaohui1, Chen Guangjie2, Christos C. Zouboulis3, Ju Qiang1   

  1. 1Department of Dermatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China; 2Department of Immunology and Microbiology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; 3Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodore Fontane, Dessau 06847, Germany
  • Received:2020-10-15 Revised:2020-11-18 Published:2021-05-31
  • Contact: Ju Qiang E-mail:qiangju401@sina.com
  • Supported by:
    National Natural Science Foundation of China （81874247, 81903234）; Scientific Research Project of Shanghai Science and Technology Commission （19ZR1431300）; Scientific Research Project of Shanghai Health and Family Planning Commission （20184Y0160）

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摘要： 【摘要】 目的 研究白藜芦醇对苯并芘诱导的SZ95人皮脂腺细胞炎症因子及相关基因表达的影响。方法 SZ95人皮脂腺细胞分为对照组、1 × 10-5 mol/L白藜芦醇组、1 × 10-5 mol/L苯并芘组及白藜芦醇 + 苯并芘组。实时荧光定量PCR检测各组SZ95人皮脂腺细胞中白细胞介素1α（IL-1α）、IL-6、芳香烃受体（AhR）、细胞色素酶P450（CYP）1A1、CYP1B1 mRNA表达；Western印迹检测各组p38丝裂原活化蛋白激酶（MAPK）磷酸化水平（磷酸化p38水平/p38水平）和AhR蛋白相对水平；酶联免疫吸附法检测各组细胞上清液中IL-1α、IL-6蛋白表达。多组间均数比较用单因素方差分析，组间两两比较采用LSD-t检验。结果 对照组、白藜芦醇组、苯并芘组及白藜芦醇 + 苯并芘组SZ95人皮脂腺细胞IL-1α的mRNA（2.045 ± 0.272、2.058 ± 0.154、3.124 ± 0.094、2.185 ± 0.337）和蛋白（9.132 ± 1.181、9.429 ± 0.771、20.361 ± 0.907、9.917 ± 0.897）表达水平差异均有统计学意义（F值分别为14.662、101.705，P值分别 < 0.01、 < 0.001），其中白藜芦醇 + 苯并芘组IL-1α mRNA和蛋白相对水平低于苯并芘组（均P < 0.01）。此外，苯并芘组p38磷酸化水平显著高于对照组、白藜芦醇组及白藜芦醇 + 苯并芘组（F = 303.129，均P < 0.000 1）。白藜芦醇 + 苯并芘组AhR、CYP1A1和CYP1B1的mRNA表达较苯并芘组显著下调（t值分别为10.640、33.599、18.327，均P < 0.001）。苯并芘组细胞AhR蛋白表达低于白藜芦醇 + 苯并芘组（P < 0.001）。结论 白藜芦醇可抑制环境污染物苯并芘诱导的SZ95人皮脂腺细胞炎症因子IL-1α表达，该作用可能通过AhR和p38MAPK通路所介导。

关键词: 皮脂腺, 痤疮, 苯并芘, p38丝裂原活化蛋白激酶类, 白细胞介素1α, 白藜芦醇, SZ95人皮脂腺细胞, 芳香烃受体

Abstract: 【Abstract】 Objective To investigate the effect of resveratrol on the expression of inflammatory cytokines and related genes in human SZ95 sebocytes induced by benzo（a）pyrene. Methods Human SZ95 sebocytes were cultured in vitro, and divided into 4 groups: control group treated with 1‰ dimethyl sulfoxide for 27 hours, resveratrol group treated with 1 × 10-5 mol/L resveratrol for 24 hours, benzo（a）pyrene group treated with 1 × 10-5 mol/L benzo（a）pyrene for 3 hours, resveratrol + benzo（a）pyrene group treated with 1 × 10-5 mol/L resveratrol for 24 hours followed by 1 × 10-5 mol/L benzo（a）pyrene for 3 hours. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of interleukin（IL）-1α, IL-6, aryl hydrocarbon receptor （AhR）, cytochrome P4501A1（CYP1A1） and cytochrome P4501B1（CYP1B1） in SZ95 sebocytes in the above groups; Western blot analysis was conducted to determine the phosphorylation level of p38 mitogen-activated protein kinase （p38 MAPK, expressed as the ratio of phosphorylated to total p38 MAPK） and AhR protein expression; enzyme-linked immunosorbent assay （ELISA） was conducted to detect levels of IL-1α and IL-6 in the cell culture supernatant in each group. One-way analysis of variance was used for comparison of means among multiple groups, and least significant difference-t test was used for multiple comparisons. Results The mRNA and protein expression of IL-1α in SZ95 sebocytes significantly differed among the control group, resveratrol group, benzo（a）pyrene group and resveratrol + benzo（a）pyrene group （mRNA: 2.045 ± 0.272, 2.058 ± 0.154, 3.124 ± 0.094, 2.185 ± 0.337, protein: 9.132 ± 1.181, 9.429 ± 0.771, 20.361 ± 0.907, 9.917 ± 0.897, F = 14.662, 101.705, P < 0.01, < 0.001, respectively）, and were significantly lower in the resveratrol + benzo（a）pyrene group than in the benzo（a）pyrene group （both P < 0.01）. In addition, the phosphorylation level of p38 was significantly higher in the benzo（a）pyrene group than in the control group, resveratrol group and resveratrol + benzo（a）pyrene group （F = 303.129, P < 0.000 1）. The mRNA expression of AhR, CYP1A1 and CYP1B1 was significantly lower in the resveratrol + benzo（a）pyrene group than in the benzo（a）pyrene group （t = 10.64, 33.599, 18.327, respectively, all P < 0.001）. The benzo（a）pyrene group showed significantly decreased protein expression of AhR compared with the resveratrol + benzo（a）pyrene group （P < 0.001）. Conclusion Resveratrol can inhibit the environmental pollutant benzo（a）pyrene-induced expression of inflammatory factor IL-1α in SZ95 sebocytes, which is likely mediated by the AhR and p38MAPK pathways.

Key words: Sebaceous glands, Acne, Benzo（a）pyrene, p38 Mitogen-activated protein kinases, Interleukin-1alpha, Resveratrol, Human SZ95 sebocytes, Aryl hydrocarbon receptor