基于NF-κB/MAPK 通路探讨微量元素锌对变应性鼻炎免疫反应的保护作用和机制研究

变应性鼻炎(AR)是由多种炎性介质介导的鼻粘膜慢性非炎症性疾病。目前发病机制不清，治疗缺乏特异性方法，现研究的焦点是明确其发病机制并寻找安全有效的治疗方案。本课题组前期基础研究显示锌参与AR的发生发展过程，并且我们的临床研究显示锌辅助治疗能明显改善AR患者的症状及体征；同时近期有研究表明锌可通过调控NF-κB/MAPK通路的表达从而影响免疫反应。故本课题组提出假说：微量元素锌可通过调控NF-κB/MAPK通路干预AR的免疫反应过程。我们将建立锌缺乏、锌正常、锌过量、缺锌补锌AR小鼠模型；体外培养小鼠肥大细胞株，采用ELISA、Westernblot等技术，检测参与免疫反应的炎性因子水平及信号通路表达情况，拟阐明锌在AR的发生发展过程中对免疫反应的保护作用，并揭示锌在NF-κB/MAPK通路中的介导机制；在此基础上，进一步证实补充锌对AR的治疗效应，将为AR的精准治疗提供理论基础和实验依据。

Allergic rhinitis (AR) is a nasal mucosa chronic non inflammatory disease resulted from various inflammatory mediators. At present, the pathogenesis of AR is not clear, so the treatment is lack of specific methods. The focus of the present study is to clarify its pathogenesis and find safe and effective therapeutic regimen.Our previous study showed that zinc plays an important role in the occurrence and development of AR, and our clinical study showed that zinc adjuvant therapy can significantly improve the symptoms and signs of patients with AR. At the same time, recent studies have shown that zinc can affect the immune reaction by regulating the expression of NF-κB/MAPK pathway.Based on the above evidence, we hypothesizes that trace element zinc can interfere the immune reaction process of AR by regulating the NF- kappa B/MAPK pathway.We will establish AR mouse models for zinc deficiency, normal zinc, zinc excess and zinc supplementation, and cultivate mouse mast cell lines in vitro. We will detect the levels of inflammatory factors involved in the immune reaction and signaling pathway expression by using ELISA and Westernblot technology.We aims to elucidate the protective effect of zinc on immune reaction in the occurrence and development of AR and to reveal the mediated mechanism of zinc in NF- kappa B/MAPK pathway. On this basis, we will further confirm the therapeutic effect of zinc supplementation on AR, which will provide theoretical and experimental basis for the accurate treatment of AR.