基于Th1/Th2、Th17/Treg细胞失衡理论的银屑病中医辨证分型免疫学机制研究

Psoriasis is a common inflammatory skin disease. The lymphocytes which mainly include T helper cells (Th) play an important role in the pathogenesis of psoriasis. Th1/Th2 drift theory is a conventional view of psoriasis immunological pathogenesis. Recently, the Th17/Treg imbalance theory has become hot and aporia in the research field . .The traditional Chinese medicine has a unique perspective and a good clinical effect for the treatment of psoriasis . Syndrome differentiation is a key factor in guiding TCM diagnosis , but its mechanism has not been elucidated yet. Our previous study is to understand the Th1/Th2 imbalance in the pathogenesis of psoriasis with blood-heat syndrome , and to explore the immunological mechanism of cooling blood detoxification in treating this kind of syndrome. In this study, we will detect the amount of Th1, Th2, Th17 and Treg cells in the peripheral blood of psoriasis patients with different syndromes, and also the expression of transcription factors and downstream factors of these cells, and then we will analyze whether there is a correlation between these results and TCM syndrome differentiation. We hope to further clarify the immunological mechanism of TCM Syndrome differentiation in the treatment of psoriasis,and provide a theoretical basis and experimental support for treating psoriasis with traditional Chinese medicine, and also provide new ideas for the treatment of other immune-related skin diseases with traditional Chinese medicine.

银屑病是常见的炎症性皮肤病，辅助性T细胞（Th）为主的淋巴细胞在银屑病发生发展中起着重要作用。Th1/Th2漂移理论是银屑病免疫学发病机制的传统观点，但近年来发现的Th17/Treg失衡现象成为该领域研究的热点和难点。中医药对治疗银屑病有着独到的见解和良好的临床疗效，辨证分型是指导中医诊疗的关键因素，但其现代医学机制尚未阐明。我们前期研究了银屑病血热证Th1/Th2失衡机制，并初步探讨了凉血解毒法治疗银屑病血热证的免疫学机制。本研究拟通过检测不同证型的银屑病患者外周血Th1、Th2、Th17、Treg细胞值，及其转录因子和下游因子的表达，与银屑病中医证型进行相关性分析，以期进一步的阐明银屑病中医辨证分型的免疫学机制，为银屑病的中医辨证论治提供理论依据和实验支持，同时也为中医药治疗其他免疫相关性皮肤病的研究提供新的思路。

本研究首先从银屑病发病的核心病理机制T细胞异常分化出发，探究银屑病中医证型的客观物质基础，结果提示：血热证是以Th1、Th17细胞分化优势伴随Th2及Treg下调为免疫学特性，Th1细胞在血热证中对临床病情有预测作用。血瘀证以Th1及Th17细胞分化优势同时伴随Th2细胞下调为免疫学特性，Treg细胞在血瘀证中不具有重要意义。血虚证Th2与Treg细胞下调为免疫学特性，Th1及Th17细胞在血虚证中不具有重要意义。银屑病血热证、血瘀证、血虚证中均出现了Th1/Th2及Th17/Treg平衡的偏移，银屑病各证型Th1/Th2、Th17/Treg、Th17/Th2比值与正常人比较, 结果提示三证型Th1/Th2、Th17/Th2比值较正常人显著升高，其严重程度呈现血瘀证>血热证>血虚证的趋势；三证型Th17/Treg比值较正常人显著升高，其严重程度呈现血热证>血瘀证>血虚证的趋势。银屑病血热证、血瘀证、血虚证均有Th2细胞免疫功能的下降。Th1、Th2细胞比例可作为评价银屑病临床病情的客观指标；Th1与Treg细胞在外周血中的含量可影响患者的生活质量评分。故此我们可以推断银屑病以“血分论治”与Th细胞的分化有一定的相关性，银屑病的各证型可能处于不同的免疫状态中，Th细胞及其相关因子的检测可在一定程度上反应各证型的生物学特性。免疫细胞紊乱是银屑病发病的重要因素。在此基础上，为了进一步的研究实银屑病发病中的关键信号通路JAK/STAT在Th细胞异常分化的银屑病病理过程中发挥重要作用，我们进行了小样本深入研究，研究结果显示：银屑病患者PBMC中通路因子pSTAT4/STAT4、pSTAT3/STAT3表达量增加，血热证、血瘀证、血虚证均明显高于正常人，血热证又高于血瘀证和血虚证；Th1与pSTAT4/STAT4呈极明显正相关，pSTAT4/STAT4与T-bet呈极明显正相关；Th17与ROR-γt呈正相关，Th17与pSTAT3/STAT3的表达呈正相关，pSTAT3/STAT3与ROR-γt呈明显正相关。上述研究结果为我们进一步深入研究不同证型的银屑病的辨证论治提供了分子免疫学基础。