基于AMPK/p38MAPK/NF-κB通路探究湿润烧伤膏改善咪喹莫特诱导小鼠银屑病样的机制研究  

Mechanism of Moist Exposed Burn Ointment on Imiquimote-Induced Psoriasis in Mice through AMPK/p38MAPK/NF-κB Pathway

作　　者：门钟兰 黄竹芸 章彦文 褚付奥 孙语迪 孙双勇 MEN Zhonglan;HUANG Zhuyun;ZHANG Yanwen;CHU Fuao;SUN Yudi;SUN Shuangyong(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Medical University,Tianjin 300070,China;Jinyao Pharmaceutical Co.,Ltd,Tianjin 300462,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津医科大学,天津300070 [3]津药药业股份有限公司,天津300462

出　　处：《中国药物评价》2025年第1期21-27,共7页Chinese Journal of Drug Evaluation

基　　金：天津市科技局创新药物和医疗器械科技重大专项(4ZXYXSY00130;一种治疗银屑病的新型TYK2抑制剂的1类新药临床前研发);国家自然科学基金项目(32170110)。

摘　　要：目的:采用咪喹莫特(imiquimod,IMQ)诱导的银屑病样小鼠模型和白细胞介素-17A(interleukin-17A,IL-17A)诱导的人角质形成细胞(HaCaT)银屑病样模型,研究湿润烧伤膏(moist exposed burn ointment,MEBO)对银屑病的治疗作用和干预机制。方法:体内实验采用IMQ诱导BALB/c小鼠建立银屑病样模型,连续6 d MEBO干预后,评估小鼠皮损情况(PASI评分)和脾脏指数,H&E染色观察皮肤组织病理学变化,ELISA检测皮肤中银屑病相关细胞因子,Western blot检测AMPK/p38MAPK/NF-κB通路蛋白的表达。体外实验利用IL-17A诱导HaCaT细胞模拟银屑病样角质形成细胞模型,MTS评估MEBO对细胞增殖的影响,ELISA检测IL-6和IL-1β的表达水平,Western blot检测AMPK/p38MAPK/NF-κB蛋白的表达。结果:与模型组比较,MEBO干预显著改善小鼠银屑病样皮损症状,降低PASI评分和脾脏指数,减轻皮损病理损伤,降低皮损中银屑病相关细胞因子的水平,下调p-NF-κB和p-p38MAPK蛋白表达水平,上调p-AMPK蛋白表达水平;体外细胞模型中,与模型组比较,MEBO能够抑制细胞增殖,降低IL-6、IL-1β表达及p-p38MAPK、p-NF-κB蛋白表达水平,激活p-AMPK蛋白表达。结论:湿润烧伤膏通过p38MAPK/NF-κB/AMPK通路抑制IL-23/Th17轴介导的炎症反应,降低炎性细胞因子水平,改善小鼠银屑病样症状。Objective:To investigate the therapeutic effect and intervention mechanism of Moist Exposed Burn Ointment(MEBO)on psoriasis,imiquimod(IMQ)-induced psoriasis-like mouse model and interleukin-17A(IL-17A)-induced psoriasis-like model of human keratinocyte-forming cells(HaCaT)were used.Methods:In vivo experiments were performed using IMQ-induced BALB/c mice to establish a psoriasis-like mouse model.After 6 consecutive days of MEBO intervention,mice were evaluated for skin lesions(psoriasis lesion area and disease severity scores)and splenic index.Hematoxylin-eosin staining was used to observe the histopathologic changes in the skin.Enzyme-linked immunosorbent assay was used to detect psoriasis-related cytokines in the skin.Western blot was used to detect the expression of AMPK/p38MAPK/NF-κB pathway proteins.For in vitro experiments,IL-17A was utilized to induce HaCaT cells to mimic a psoriasis-like keratinocyte model.MTS was used to assess the effect of MEBO on cell proliferation.The expression levels of IL-6 and IL-1βwere detected by enzyme-linked immunosorbent assay.Western blot was used to detect the expression of AMPK/p38MAPK/NF-κB proteins.Results:Compared with the model group,MEBO intervention significantly improved the symptoms of psoriasis-like skin lesions,reduced PASI score and spleen index,and attenuated the pathological damage of skin lesions in mice.MEBO reduced the levels of psoriasis-related cytokines in skin lesions,down-regulated the levels of p-NF-κB and p-p38MAPK protein expression,and up-regulated the levels of p-AMPK protein expression.In the in vitro cell model,compared with the model group,MEBO could inhibit cell proliferation and reduce IL-6 and IL-1βexpression.At the same time,MEBO could reduce p-p38MAPK and p-NF-κB protein expression levels and activate p-AMPK protein expression.Conclusion:MEBO can inhibit the suppression of IL-23/Th17 axis-mediated inflammatory response through the p38MAPK/NF-κB/AMPK pathway,reduce the level of inflammatory cytokines,and ameliorate psoriasis-like sym

关 键 词：银屑病 湿润烧伤膏 咪喹莫特 IL-17A IL-23/Th17 

分 类 号：R965.1[医药卫生—药理学]