芹菜素对咪喹莫特诱导的小鼠银屑病样皮损的影响及机制  

Effect and mechanism of apigenin in treating IMQ-induced psoriasiform lesions:an analysis based on a flaky skin mouse model

作　　者：马楚君 阮彬家 鲁人玮 连盼盼 王文彤 王宏伟[2] 苏忠兰[1] 鲁严[1] MA Chujun;RUAN Binjia;LU Renwei;LIAN Panpan;WANG Wentong;WANG Hongwei;SU Zhonglan;LU Yan(Department of Dermatology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;State Key Laboratory of Analytical Chemistry for Life Science&Jiangsu Key Laboratory of Molecular Medicine,Medical School of Nanjing University,Nanjing 210093,China)

机构地区：[1]南京医科大学第一附属医院皮肤性病科,江苏南京210029 [2]南京大学医学院生命分析化学国家重点实验室&江苏省分子医学重点实验室,南京大学医学院,江苏南京210093

出　　处：《临床皮肤科杂志》2023年第8期455-461,共7页Journal of Clinical Dermatology

基　　金：国家自然科学基金面上项目(81872541);国家自然科学基金面上项目(82273549);国家自然科学基金面上项目(81773326)资助项目。

摘　　要：目的:观察芹菜素对咪喹莫特(IMQ)造模小鼠及对角质形成细胞(HaCaT细胞)炎症通路和细胞增殖的影响。方法:小鼠随机分为4组,连续6 d使用凡士林或IMQ涂抹背部皮肤建立对照组和银屑病模型,期间每日予芹菜素或玉米油灌胃。于第7天比较治疗后各组皮损变化;蛋白免疫印迹法(western blot)检测各组核因子κB抑制蛋白(IKB)α、磷酸化(phosphorylation,p)-IKBα、凋亡及细胞核因子-κB p65(NF-κB p65)、p-NF-κB p65、信号转导与转录激活因子(STAT)3、p-STAT3、细胞增殖抗原(Ki-67)和角蛋白(keratin,K)17蛋白变化。体外实验设对照组、模型组、5μmol/L芹菜素处理组和10μmol/L芹菜素处理组;western blot检测各组角质形成细胞p-STAT3、STAT3、p-IKBα、IKBα、p-NF-κB p65、NF-κB p65、Ki-67和K17变化。结果:芹菜素改善了IMQ诱导的银屑病样小鼠的皮损及病理改变。与造模组比较,干预组小鼠皮损中p-STAT3、p-IκB、p-NF-κB p65、Ki-67、K17和NOD样受体热蛋白结构域相关蛋白(NLRP)3表达量显著下降(P<0.05)。细胞模型中,与模型组相比,5μmol/L芹菜素显著抑制(P<0.05)p-IKBα、p-NF-κB p65、Ki-67和K17的表达;10μmol/L芹菜素显著抑制(P<0.05)p-STAT3、p-IKBα、p-NF-κB p65、Ki-67和K17的表达。芹菜素以剂量依赖方式抑制NLRP3的表达。结论:芹菜素可以缓解IMQ诱导的小鼠银屑病样皮损。在小鼠和细胞模型中,芹菜素对STAT3的磷酸化、NF-kappa B通路的激活、Ki-67的表达和K17的表达有明显的抑制作用,其可能通过抑制NLRP3的表达实现。Objective:To analyze the effects of apigenin on inflammatory pathways and cell proliferation in a mouse model of psoriasis induced by imiquimod(IMQ)and HaCaT.Methods:Mice were randomly divided into four groups,and petroleum jelly or IMQ was applied to the back skin for six consecutive days to establish a control or psoriasis model,during which they were given daily apigenin or corn oil gavage.At day 7 after treatment,the changes of skin lesions in each group were compared.Western blotting was used to detect the expression of skin proteins p-IKBα、IKBα、p-NF-κB p65、NF-κB p65、p-STAT3、STAT3、Ki-67 and K17 in each group.The efficacy was evaluated in normal group,model group,5μmol/L apigenin group and 10μmol/L apigenin group.Western blot was used to detect changes of p-STAT3、STAT3、p-IKBα、IKBα、p-NF-κB p65、NF-κB p65、Ki-67 and K17 in various groups of keratinocytes.Results:Apigenin alleviated the psoriasis-like phenotype and pathological changes induced by IMQ in mice.Compared to the model group,the intervention group showed significant reductions(P<0.05)in the expression levels of p-STAT3,p-IκB,p-NF-κB p65,Ki-67,K17,and NLRP3 in the mouse skin lesions.In the cell model,compared to the model group,5μM apigenin did not significantly changed p-STAT3 expression,but significantly inhibited(P<0.05)the expression of p-Iκ-Bα,p-NF-κB p65,Ki-67,and K17.On the other hand,10μM apigenin significantly inhibited(P<0.05)the expression of p-STAT3,p-IκBα,p-NF-κB p65,Ki-67,and K17.Apigenin inhibited the expression of NLRP3 in a dose-dependent manner.Conclusion:Oral apigenin may significantly relieve IMQ-induced psoriasis-like lesions.In mouse and cellular models,apigenin has an inhibitory effects on phosphorylation of STAT3,activation of NF-kappa B pathway,expression of Ki-67 and expression of K17.These effects may be achieved by inhibiting the expression of NLRP3.

关 键 词：银屑病 芹菜素 HACAT细胞 咪喹莫特 NOD样受体热蛋白结构域相关蛋白 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]