基于银屑病血燥证“燥湿互化，湿毒内生”研究养血解毒方对Stat3介导的γδT-KC相互作用的分子机制

银屑病皮损真皮处γδ T细胞和角质形成细胞（KC）反馈环路相互激发，使IL-17为主的细胞因子群落参与持续的免疫应答，其中Stat3通路活化是炎症持续存在的重要基础。血燥证型病程绵长，经久不愈，为临床治疗难点，病机主要为燥湿互化，湿毒内生，致津液敷布异常，与银屑病病理生理变化密切相关。临床以养血解毒为法，养血解毒方显示良好的临床疗效。研究证实该方明显改善临床症状和银屑病样小鼠皮损、抑制IL-17类细胞因子分泌和pSTAT3表达。因此本项目将进一步研究其对Stat3转基因小鼠银屑病样皮损γδ T细胞、KC活化分化异常与Stat3通路调控和表皮屏障功能的作用，明确干预环节；并体外观察养血活血、祛湿解毒组分分别对诱导的高表达Stat3的IL-17+γδ T细胞、高表达Stat3的KC的活化及通路蛋白表达的影响，揭示作用靶点，从动物、细胞、分子水平阐明银屑病血燥证的病机基础，为临床治疗提供科学依据

The mutual activation among γδ T-KC feedback loop by IL-17 stimulation in psoriasis lesion keep the immune response persist exist, in which STAT3 pathway abnormal activation play an important role in inflammation persistent. The blood-dryness differention of psoriasis attracted more attention for its long disease course and difficulty to cure. We proposed the hypothesis that blood-dryness is formed by internal dampness-poison deposition caused by abnormal transformation between dampness and dryness, by which body fluid distribution in skin is arrested and skin injury developed. It is related to pathological and physiological process of psoriasis. In clinical, nourishing blood and detoxification is the principle and Yang xue jie du(YXJD) prescription is an effective prescription. Formal studies approved that the prescription obviously improved clinical symptoms and ameliorated mice psoriasis-like lesion. Meanwhile, it inhabited Th17 cytokines secretion and suppressed pSTAT3 expression. In this project we will focus on the effect of YXJD prescription on STAT3 transgenic mice, and study the intervention onγδ T-KC loop, STAT3 pathway activation and epidermal barrier function, in order to clarify the possible targets of YXJD prescription. In vitro study, we will observe separately ‘Yang xue huo xue’ and ‘qu shi jie du’ components on the effect of γδ T and KC with STAT3 over-expression induced by stimulators, and its mutual influence and related pathway signal molecules expression, by which we explore the possible therapeutic targets of YXJD prescription from animal model, cells and molecular levels and provide scientific evidence for clinical treatment.