锦菊素对银屑病模型小鼠的药效学作用及其机制探究  

Mechanism of bigelovin in treatment of imiquimod-induced psoriasiform mouse model

作　　者：张悦 陆奕 杨婧雯 王钰凯 张梦莹 周芳[2] 王广基[2] 许正新[1,3] ZHANG Yue;LU Yi;YANG Jing-wen;WANG Yu-kai;ZHANG Meng-ying;ZHOU Fang;WANG Guang-ji;XU Zheng-xin(Dept of Pharmacology,School of Medicine,Yangzhou University,Yangzhou,Jiangsu 225000,China;Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics,Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences,China Pharmaceutical University,Nanjing 210009,China;the Key Laboratory of Basic and Clinical Transformation of Noncoding RNA,Jiangsu Province,Yangzhou,Jiangsu 225000,China)

机构地区：[1]扬州大学医学院药理学教研室,江苏扬州225000 [2]中国药科大学,江苏省药物代谢动力学重点实验室,中国医学科学院“中药复杂组分PK-PD结合研究”创新单元,江苏南京210009 [3]江苏省非编码RNA基础与临床转化重点实验室,江苏扬州225000

出　　处：《中国药理学通报》2022年第12期1801-1808,共8页Chinese Pharmacological Bulletin

基　　金：中国医学科学院医学与健康科技创新工程项目(No 2021-I2M-5-011);深圳市三名工程项目(No SZSM201801060)。

摘　　要：目的探讨锦菊素对咪喹莫特诱导的银屑病模型小鼠的药效作用及其机制。方法建立咪喹莫特乳膏涂抹小鼠背部皮肤诱导的银屑病模型,以皮损面积及严重程度指数、病理学和炎症因子水平及相关分子生物学数据的变化作为效应学指标,观察不同浓度的锦菊素给药后以上参数的变化并分析其可能的作用机制。结果与模型组相比,锦菊素可明显改善咪喹莫特诱导的小鼠皮肤红斑、鳞屑、增厚等症状,PASI评分明显降低;组织病理学相关指标显示,锦菊素干预组能够剂量依赖性地减轻小鼠表皮增厚情况,降低表皮细胞中Ki67的表达水平。炎症因子及分子生物学结果表明,锦菊素干预组小鼠皮肤组织中S100a8、S100a9、IL-17A、IL-6、IL-1β表达降低,血清中IL-2、IL-4、TNF-α、IFN-γ及IL-17A表达降低。淋巴结中Th17细胞比例降低,Treg细胞比例增加。此外,锦菊素还能够下调咪喹莫特诱导的P65蛋白磷酸化水平升高,显著抑制P65入核,提示锦菊素能够抑制咪喹莫特诱导的P65蛋白活化。结论锦菊素能够改善咪喹莫特诱导的银屑病模型小鼠的症状和体征,该项作用可能与抑制角质细胞中P65蛋白磷酸化相关。Aim To investigate the effects of bigelovin on mouse model of imiquimod-induced psoriatic itch and its mechanism.Methods Psoriasis-like mouse model was established by applying imiquimod cream on the back skin of mouse.Psoriasis area and severity index,pathological changes,the expression levels of inflammatory factors and related molecular biological data were used as effect indicators.The changes of the above parameters were observed after administration of different concentrations of bigelovin.Then the possible mechanism of the effects was further analysed.Results Compared with the model group,bigelovin significantly decreased the symptoms of skin lesions and reduced the PASI score.Bigelovin alleviated epidermal thickening and reduced the expression of Ki67 in a dose-dependent manner.The expression levels of inflammatory factors were reduced in both skin and serum.The percentage of Th17 cells was reduced and the percentage of Treg cells was increased in the lymph node.In addition,bigelovin also inhibited the phosphorylation of P65 protein and significantly reduced the nuclear localization of P65,suggesting that bigelovin might inhibit the activation of P65 protein.Conclusions The effect of bigelovin on improving the signs and symptoms of imiquimod-induced psoriasis mice may be related to the inhibition of P65 protein phosphorylation in keratinocytes.

关 键 词：锦菊素 银屑病 咪喹莫特 TH17细胞 TREG细胞 炎症 

分 类 号：R-332[医药卫生] R284.1R322.99R392.12R758.63