摘要
目的本研究旨在探讨GS-9620通过调控Th1/Th17相关免疫反应改善咪喹莫特(IMQ)诱导的银屑病样炎症的作用机制,并进一步研究其对小鼠肠道菌群的调节作用。方法采用BALB/c小鼠建立IMQ诱导的银屑病样炎症模型,通过PASI评分评估皮损严重程度,利用流式细胞术检测脾组织CD4^(+)IL-17^(+)和CD4^(+)IFN-γ^(+)细胞比例,采用ELISA法测定皮肤组织中TNF-α、IL-1β和IL-6等炎症因子水平,并通过苏木素-伊红(HE)染色进行病理学分析。进一步对正常组、IMQ组和IMQ+GS-9620组小鼠的肠道菌群进行16S rRNA测序,分析GS-9620对肠道菌群结构的影响。结果GS-9620显著降低了IMQ诱导小鼠的PASI评分,并有效抑制了脾中CD4^(+)IL-17^(+)和CD4^(+)IFN-γ^(+)细胞比例。同时,GS-9620显著下调了皮肤组织中TNF-α、IL-1β和IL-6的表达水平。16S rRNA测序分析显示,GS-9620可显著调节与炎症相关的肠道菌群丰度,包括毛螺菌属(Lachnospiraceae_NK4A136_group和Lachnospiraceae_UCG-008)、拟普雷沃氏菌属(Alloprevotella)、脱硫弧菌属(Desulfovibrio)、普雷沃氏菌属(Prevotellaceae_UCG-001)和另枝菌属(Alistipes)等菌属的相对丰度。结论GS-9620通过调控Th1/Th17相关炎症因子的表达,有效缓解IMQ诱导的小鼠银屑病样皮肤炎症。此外,其可能通过调节肠道菌群结构来改善IMQ诱导的临床症状,这为通过菌群调节治疗银屑病提供了新的理论依据。本研究结果为进一步探索GS-9620在银屑病治疗中的应用价值提供了重要的实验依据。
Objective To explore the mechanism of GS-9620 in improving imiquimod(IMQ)-induced psoriasis-like inflammation by regulating the Th1/Th17-related immune response,and to investigate its regulatory effect on the gut microbiota in mice.Methods An IMQ-induced psoriasis-like inflammation model was established in BALB/c mice.The severity of the skin lesions was evaluated by psoriasis area and severity index(PASI)score.The proportions of CD4^(+)interleukin(IL)-17^(+)and CD4^(+)interferon(IFN)-γ^(+)cells in spleen tissue were detected by flow cytometry.Levels of the inflammatory factors tumor necrosis factor(TNF)-α,IL-1β,and IL-6 in skin tissues were determined by enzyme-linked immunosorbent assay,and pathological analysis was performed by hematoxylin/eosin staining.The effects of GS-9620 on the structure of the gut microbiota in control,IMQ model,and GS-9620-treated mice were detected by 16S rRNA sequencing.Results GS-9620 significantly reduced the PASI score in IMQ-induced mice and effectively reduced the proportions of CD4^(+)IL-17^(+)and CD4^(+)IFN-γ^(+)cells in the spleen.GS-9620 also significantly down-regulated the expression levels of TNF-α,IL-1β,and IL-6 in skin tissues.16S rRNA sequencing showed that GS-9620 significantly regulated the abundance of gut microbiota related to inflammation,including the relative abundances of bacteria such as Lachnospiraceae_NK4A136_group,Lachnospiraceae_UCG-008,Alloprevotella,Desulfovibrio,Prevotellaceae_UCG-001,and Alistipes.Conclusions GS-9620 effectively alleviates IMQ-induced psoriasis-like skin inflammation in mice by regulating the expression of Th1/Th17-related inflammatory factors.It may also improve IMQ-induced clinical symptoms by regulating the structure of the gut microbiota,thus providing a new theoretical basis for the treatment of psoriasis.The result of this study provide important experimental evidence to support further investigations into the application of GS-9620 for the treatment of psoriasis.
作者
杨婧宇
张倩
陈思
王晓堂
宋国华
YANG Jingyu;ZHANG Qian;CHEN Si;WANG Xiaotang;SONG Guohua(Laboratory Animal Center,Shanxi Medical University,Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model,Taiyuan 030001,China;Department of Dermatology,Shenzhen Nanshan People’s Hospital,Shenzhen 518052,China;Department of Immunology,Shenzhen University Medical School,Shenzhen 518000,China)
出处
《中国实验动物学报》
北大核心
2025年第7期1021-1031,共11页
Acta Laboratorium Animalis Scientia Sinica
基金
深圳市科技研发资金(JCYJ20220530141615035)
实验动物新资源创制与利用山西省科技创新人才团队(202204051002032)。
关键词
银屑病
银屑病样炎症小鼠模型
肠道菌群
GS-9620
16S
rRNA
psoriasis
psoriasis-like inflammation animal models
gut microbiota
GS-9620
16S rRNA Conflicts of Interest:The authors declare no conflict of interest
