中国药物评价2025，Vol.42Issue(1)：21-27,7.
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
摘要
Abstract
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 estab-lish 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-1 βwere detected by enzyme-linked immunosorbent assay.Western blot was used to detect the expression of AMPK/p38MAPK/NF-κB pro-teins.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 psoria-sis-related cytokines in skin lesions,down-regulated the levels of p-NF-κB and p-p38MAPK protein expression,and up-regulated the lev-els 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-1β expression.At the same time,MEBO could reduce p-p38MAPK and p-NF-κB protein expression levels and acti-vate 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 symptoms in mice.关键词
银屑病/湿润烧伤膏/咪喹莫特/IL-17A/IL-23/Th17Key words
Psoriasis/Moist exposed burn ointment/Cytokines/IL-17A/IL-23/Th17分类
药学引用本文复制引用
门钟兰,黄竹芸,章彦文,褚付奥,孙语迪,孙双勇..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[J].中国药物评价,2025,42(1):21-27,7.基金项目
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) （32170110）
