雷公藤红素通过调控Ezrin的活化改善特应性皮炎  

Celastrol ameliorates atopic dermatitis by modulating Ezrin activation

作　　者：金泓宇 王丹丹 宋昕怡 徐可欣 延光海 李良昌 JIN Hong-yu;WANG Dan-dan;SONG Xin-yi;XU Ke-xin;YAN Guang-hai;LI Liang-chang(Key Laboratory of Immunization and Targeting Research on Common Allergic Diseases in Jilin Province,Yanji Jilin 133002,China)

机构地区：[1]吉林省过敏性常见疾病免疫与靶向研究重点实验室,吉林延吉133002

出　　处：《中国药理学通报》2024年第10期1921-1930,共10页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81970018,82060008);吉林省科技厅项目(No YDZJ202201ZYTS140)。

摘　　要：目的探究雷公藤红素(Celastrol)对DNCB致敏诱导特应性皮炎(atopic dermatitis,AD)小鼠组织及HaCaT细胞中Ezrin表达的影响。方法取BALB/c小鼠,随机分为Control、DNCB组、Celastrol 25μg、50μg、75μg治疗组、Dex组,每组8只;HaCaT细胞用TNF-α诱导,并用1μmol·L^(-1)Celastrol及Ezrin siRNA治疗。测厚仪测量小鼠耳部及背部皮肤厚度,取小鼠脾及淋巴结观察其变化。采用HE及甲苯胺蓝染色法观察小鼠炎症细胞浸润及肥大细胞脱颗粒情况。利用流式细胞仪检测小鼠淋巴结中IL-4及TNF-α水平,酶联免疫吸附剂测定小鼠血清中IL-4、TNF-α、IgE水平,HaCaT细胞上清液中IL-4、IL-5及IL-13的表达。Western blot检测皮肤组织P-Ezrin、Ezrin的表达。结果Celastrol明显抑制小鼠耳部及背部皮肤组织肿胀程度,减轻炎症细胞浸润及肥大细胞脱颗粒情况,降低小鼠血清中IgE及血清、淋巴结中IL-4、TNF-α含量并减少的Ezrin活化。Ezrin siRNA治疗后,HaCaT细胞上清液中IL-4、IL-5及IL-13的表达得到恢复。结论Celastrol可能是通过调节Ezrin的活化实现可改善AD。Aim To investigate the effect of Celastrol on the expression of Ezrin in tissues and HaCaT cells of DNCB sensitisation-induced atopic dermatitis(AD)mice.Methods BALB/c mice were taken and randomly divided into the control,DNCB group,Celastrol 25μg,50μg,75μg treatment group,and Dex group,with 8 mice in each group;HaCaT cells were induced with TNF-αand treated with 1μmol·L^(-1) Celastrol and Ezrin siRNA.The thickness of the skin on the ear and back of mice was measured by a thickness gauge,and the spleen and lymph nodes of mice were taken to observe the changes.HE and toluidine blue staining were used to observe the inflammatory cells and mast cell infiltration in mice.Flow cytometry was used to detect the levels of IL-4 and TNF-αin the lymph nodes of mice,and enzyme-linked immunosorbent was used to determine the levels of IL-4,TNF-αand IgE in serum of mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells.Western blot was used to detect the expression of P-Ezrin and Ezrin in skin tissues.Results Celastrol significantly inhibited the swelling of ear and back skin tissues,reduced the degranulation of inflammatory cells and mast cells,lowered serum IgE and serum and lymph node levels of IL-4 and TNF-α,and reduced the activation of Ezrin in mice,and the expression of IL-4,IL-5 and IL-13 in the supernatant of HaCaT cells was restored by the treatment with Ezrin siRNA.Conclusion Celastrol ameliorates AD,which may be achieved by modulating Ezrin activation.

关 键 词：特应性皮炎 雷公藤红素 EZRIN HACAT细胞 DNCB IL-4 

分 类 号：R-332[医药卫生] R282.71R392.12R758.3