从调节Th17迁移的CCL20/CCR6轴研究凉血活血解毒方治疗银屑病血热证的作用机制

Chemokine/chemokine receptor (CCL20/CCR6) abnormal expressions lead to abnormal chemotaxis of Th17 cells and the formation of stimulation loop between Th17 cells and kerotinocyte. This is one of important foundations of persist inflammatory in psoriasis lesions. 'Entangled of the heat and toxin' is main etiology of psoriasis with blood heat syndrome. Therapy of 'Cooling blood and detoxification' and prescription of 'LiangXueHuoXueJieDu' decoction are efficient treatment. The former results have shown that 'LiangXueHuoXueJieDu' decoction regulated CCL20/CCR6 mRNA expressions in Imiquimod-induced psoriasis lesions. This study proposes to explore the CCL20/CCR6 expression pattern and the possible effect of 'LiangXueHuoXueJieDu' decoction on CCL20/CCR6 expressions and Th17 cells infiltration in psoriasis lesions from clinical research and psoriasis-like animal model. Meanwhile，further to elucidate the role of CCL20/CCR6 axis in Th17 cell migration and the stimulation loop between Th17 cells and kerotinocyte in vitro. Besides,to explore the effect of 'LiangXueHuoXueJieDu' decoction on Th17 cells chemotaxis, CCR6 expression, CCL20 and related signal molecular expressions in psoriasis-like mice and in vitro. All above are used for integrative study of 'syndrome, principle and efficiency' to enrich TCM theory of 'Cooling blood and detoxification'.

趋化因子/趋化因子受体CCL20/CCR6轴异常表达，导致Th17细胞异常迁移，并激活Th17细胞与角质形成细胞（KC）间的循环刺激网络，是引发银屑病皮损区炎症反应持续存在的重要基础。在银屑病血热证表现为血分"毒热互结"，治以凉血解毒法佐以活血，凉血活血解毒方是其有效方剂。前期研究发现该方可调节咪喹莫特诱导的小鼠银屑病样皮损CCL20/CCR6 mRNA的表达。以此为线索本课题拟从临床、动物、体外细胞三个层面研究，首先观察银屑病血热证患者皮损和小鼠银屑病样模型皮损CCL20/CCR6表达及Th17浸润数量，明确皮损区CCL20/CCR6轴的变化规律及凉血活血解毒方的干预作用。同时体外研究CCL20/CCR6轴在Th17细胞迁移及Th17细胞与KC间循环刺激环路形成过程中的介导作用，探索凉血活血解毒方的作用靶点，并通过方证对应分析，阐明银屑病血热证病机理论，为临床用药提供科学依据。