基于artemin/GFRα3信号通路探讨清热祛湿方调节 特应性皮炎温热痒觉异化的机制研究

瘙痒是特应性皮炎（AD）最突出的临床症状，治疗瘙痒是控制AD的重要基础。神经纤维表皮内增生以及瘙痒信号的神经传导异常是导致痒觉异化，痒-搔抓循环发生的重要环节。前期研究发现，依据“热微则疮痒”的中医理论，采用中药“清热祛湿方”能抑制IL-33/ST2信号传导，调节Th17/Treg免疫平衡，改善AD皮疹及瘙痒，但止痒的神经免疫机制尚不明。基于神经营养因子artemin/GFRα3信号通路是“温热”痒觉异化中关键机制的最新理论，本项目构建artemin激活的神经细胞和动物实验模型，采用免疫印迹、RT-qPCR、原位杂交、免疫组织化学等技术，从表皮内神经突生长增殖，背根神经节表达瘙痒相关受体，和脊髓内小胶质细胞活性化这三大神经传导环节，以及温热刺激下的动物行为学研究，探讨清热祛湿方对 “温热”痒觉异化的影响。通过研究，有望阐明“清热祛湿方”的止痒机制，为中医治疗AD的优越性提供新的理论依据。

Pruritus is the most prominent symptom of Atopic dermatitis (AD), thus relieve itchiness is significant in controlling AD. Nerve epidermal hyperplasia and dysregulation of itch signaling pathway are common cause of alloknesis, whereby pruritus is an important factor for constantly scratching. According to “Mild heat causes sore and pruritus” in Chinese medicine theory, preliminary research shows Qing Re Qu Shi formula is able to relieve skin lesion and itchiness in AD through inhibition of IL-33/ST2 signaling transduction and regulation of Th17/Treg balance. However, the mechanism of its antipruritic effect remains unclear. The latest studies state that neurotrophic factor artemin/GFRα3 signaling pathway involves in the mechanism of warmth-provoked alloknesis. Therefore, both artemin induced nerve cell and animal model will be introduced in our project with the aid of experimental technique such as Western blot, RT-qPCR, in situ hybridization, immunochemistry, etc. Growth in nerve epidermal, expression of receptors related to pruritus in dorsal root ganglion and spinal microglia activation will be analyzed in this project. The effect of Qing Re Qu Shi formula on warmth-provoked alloknesis is determined through the investigation of these three major nerve transmissions and animal model behavior towards heat stimulus. Thus, this research aims to clarify the mechanism of Qing Re Qu Shi formula on anti-pruritic effect, and it provides new evidence of the advantage of Chinese medicine in treating AD.