基于TLR-NF-κB通路和Thl/Th2平衡偏移对温阳益气法治疗变应性鼻炎的机制研究

Allergic rhinitis (AR) is a common frequently-occurring disease, which has greatly threatened human health and life quanlity. It’s pathogenesis is complicated, involving several signal pathways, cytokines and inflammatory mediators. As a major clinical method in Traditional Chinese Medicine (TCM), warming yang and benefiting qi (WYBQ) shows promising therapeutic effect. The previous results showed that, the effects of WYBQ on AR are through regulating NF-κB pathway, downregulating TLR4 mRNA and protein levels, and decreasing the release of Th2 cytokines. Accordingly, we hypothesize that inhibition of TLR-NF-κB pathway and regulation of Th1/Th2 balance are the possible mechanisms of WYBQ therapy on AR. In this study, we propose to detect the relative regulating proteins levels of Th1/Th2 cytokines, and TLR-NF-κB pathway by using Western blot, RT-qPCR, and microarray assays in patients with lung yang-qi deficiency syndrome, for illustrating the mechanisms of WYBQ therapeutic effect on AR through regulating NF-κB pathway and trend of Th1/Th2 bias. This study will theoretically support the use of WYBQ on AR therapy, and promoting its wide application.

变应性鼻炎是严重危害患者身体健康与生活质量的常见多发病，其发病机制较为复杂，涉及多条信号通路、细胞因子和炎症介质。中医药治疗具有疗效优势，温阳益气法是临床的主要治法。前期研究发现益气温阳法是通过调控NF-kB信号通路而发挥治疗作用的，同时发现治疗患者TLR4的mRNA水平降低，TLR4蛋白表达与Th2类因子的释放也减少。据此推测：益气温阳法治疗AR的一个重要机制是抑制TLR-NF-kB通路，纠正Th1/Th2失衡。本课题以AR肺阳气虚患者为对象，运用Western Blot、RT-PCR及芯片技术等方法，检测患者Th1/Th2细胞因子，TLR和NF-kB通路的上、下游基因、蛋白表达等指标，阐明温阳益气法治疗AR是通过调控TLR-NF-kB通路，纠正Th1/Th2平衡偏移而实现的，为该法作为临床治疗AR的重要治法提供理论依据。以此进一步推动温阳益气法在临床治疗AR的广泛应用。

本课题基本按计划顺利完成，并取得预期结果。课题以肺肾气虚型AR患者为研究对象，采用随机双盲安慰剂对照设计，通过ELISA检测、免疫组化、 Western Blot等技术，研究了益气温阳治法对肺肾气虚型AR患者Th1/Th2细胞因子IL-4、IFN-γ的影响，以及对Th2上游调节信号蛋白NF-κB p65、NF-κB p105/p50、IKB-a、TLR2、TLR4蛋白表达的影响。结果：试验组治疗后血清IL-4水平较试验组治疗前低（p<0.05），试验组治疗后血清IL-4水平比安慰剂组治疗后血清IL-4水平低。试验组治疗后鼻腔黏膜TLR2蛋白表达水平较安慰剂组治疗后低（p<0.05）｡结论：益气温阳法治疗能抑制肺肾气虚型AR患者鼻腔黏膜TLR2和TLR4水平的升高，抑制变态反应；同时降低肺肾气虚型AR患者血清IL-4水平，纠正AR患者Th1/Th2细胞因子网络的失衡状态。