升麻素经皮给药对小鼠特应性皮炎的作用机制  

The therapeutic effect of cimifugin on atopic dermatitis in mice and its mechanism

作　　者：王晓钰 王倩倩 张方辰 王杰琼[2] WANG Xiao-yu;WANG Qian-qian;ZHANG Fang-chen;WANG Jie-qiong(School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;School of Health Industry,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]山东中医药大学药学院,山东济南250355 [2]山东中医药大学健康产业学院,山东济南250355

出　　处：《中国药理学通报》2023年第9期1648-1654,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82204794);山东省医药卫生科技发展计划项目(No 202002070917);山东省中医药科技项目(No 2020Q003)。

摘　　要：目的研究升麻素经皮给药抑制异硫氰酸荧光素(fluorescein isothiocyanate,FITC)诱导的小鼠特应性皮炎(atopic dermatitis,AD)的效应,并探讨其作用机制。方法ICR小鼠随机分为空白组、模型组、地塞米松阳性药组、升麻素经皮给药低剂量组、高剂量组、升麻素灌胃组。在致敏阶段,采用FITC溶液涂抹小鼠剃毛腹部,激发阶段,采用0.6%FITC溶液攻击小鼠左右耳,给药组从致敏开始给药连续7 d。检测升麻素经皮给药对小鼠体质量、胸腺指数、脾脏指数的影响;HE染色观察耳部炎症细胞浸润;测量小鼠耳肿胀,ELISA方法检测Th2型细胞因子IL-5、IL-13以及促过敏关键启动子IL-33;免疫组化和Western blot方法检测丝聚合蛋白(filaggrin)、紧密连接蛋白-1(claudin-1)、封闭蛋白(occludin)、钙黏蛋白(E-cadherin)。结果与空白组比较,模型组小鼠可见明显AD症状,与模型组比较,升麻素经皮给药组明显减少耳部炎症细胞浸润,明显降低耳肿胀及IL-5、IL-13、IL-33的分泌,明显升高filaggrin、occludin的蛋白表达。结论升麻素经皮给药对小鼠AD抑制效果明显,其作用机制是通过修复上皮屏障功能,恢复filaggrin、occludin,抑制促过敏因子IL-33,最终抑制AD炎症。Aim To investigate the effects of cimifugin on mouse atopic dermatitis(AD)induced by fluorescein isothiocyanate(FITC)and further explore the mechanism of its action.Methods ICR mice were randomly divided into blank group,model group,positive group(dexamethasone),low dose group,high dose group and administration group of cimifugin.FITC solution was applied to the shaved abdomen of mice in the sensitization stage,and 0.6%FITC solution was applied to attack the ears of mice in the stimulation stage.The administration groups were given medicine for seven consecutive days.The effects of cimifugin on body weight,thymus index and spleen index of mice were detected.Ear inflammatory cell infiltration was observed by HE staining.The ear swelling of mice was measured,and Th2 cytokines IL-5,IL-13 and the key promoter of allergy IL-33 were detected by ELISA.The epithelial barrier structural proteins,filaggrin,claudin-1,occludin and E-cadherin,were detected by immunohistochemistry and Western blot.Results Compared with the blank group,the model group showed significant AD symptoms.Compared with the model group,cimifugin transdermal administration group significantly reduced ear inflammatory cell infiltration,ear swelling,IL-5,IL-13 and IL-33,and significantly increased the expression of filaggrin and occludin.Conclusions Transdermal administration of cimifugin could significantly inhibit AD in mice,and its mechanism involves repairing epithelial barrier function,restoring filaggrin and occludin,inhibiting allergy promoting factor IL-33,and finally inhibiting AD inflammation.

关 键 词：升麻素 经皮给药 特应性皮炎 上皮屏障 丝聚合蛋白 封闭蛋白 白介素-33 

分 类 号：R-332[医药卫生] R282.71R341R452R364.5R758.3