鼻内针法通过TRPV1途径对变应性鼻炎中CD4+T细胞增殖分化的调控机制研究

The proliferation and differentiation of CD4+T cells is the main biological event leading to the development of allergic rhinitis (AR). Transient receptor potential vanilloid-1 (TRPV1) is a newly discovered channel protein closely related to this event. Endonasal acupuncture is an innovative therapy with a long-term clinical implementation by our group. The preliminary investigation showed that this therapy did not only alleviate AR’s clinical symptoms by regulating the balance of Th1/Th2 cells and the neurogenic inflammation with involvement of the central nervous system, but also might have a neuroimmunoregulation pathway related to TRPV1. Our preliminary experiments showed that endonasal acupuncture could downregulate the expression and activity of TRPV1 and improved the immune balance of AR model animals. Thus, the proposed project will focus on the regulation mechanism of the proliferation and differentiation of CD4+T cells which is realized by endonasal acupuncture through the TRPV1 pathway, and discover the mechanism among TRPV1, neuropeptide and immune factors in AR. Through model animal experiments, in vivo experiments and in vitro experiments, we’ll systematically study the mechanism of endonasal acupuncture in AR, which is regulated by the proliferation and differentiation of CD4+T cells and further regulated by the neural-immune interaction network through the TRPV1 pathway; and explore a new strategy of AR prevention and treatment with TRPV1 pathway as the core. Our findings will provide experimental evidence and theoretical basis for the anti-inflammatory and anti-allergic mechanism of TCM acupuncture therapy.

CD4+T细胞增殖分化是导致变应性鼻炎（AR）发生的主要生物学事件，TRPV1是新近发现的与CD4+T细胞增殖分化密切相关的通道蛋白。鼻内针法为项目组长期应用临床的创新疗法。前期研究发现其不仅可改善AR临床症状、调节Th1/Th2平衡、调控中枢参与下的神经源性炎症，可能还存在TRPV1相关的免疫调控途径。我们预初实验发现：鼻内针法可下调TRPV1的表达和活性，改善AR模式动物免疫平衡。鉴此，本项目将以鼻内针法通过TRPV1途径对CD4+T细胞增殖分化的调控机制为聚焦点，通过模式动物实验、体内实验、体外实验，解析AR中TRPV1、神经肽和免疫因子间的规律，系统研究和完善鼻内针法经TRPV1途径实现对AR中CD4+T细胞增殖分化的调控，进而明晰AR中神经-免疫交互网络的具体机制，探索以鼻内针法和TRPV1为核心的防治AR新策略。为丰富中医针刺疗法抗炎抗敏机制提供实验依据和理论基础。

变应性鼻炎（AR）防治是中西医研究前沿的热点与难点，是亟待解决的慢性呼吸道难治性炎性疾病之一。CD4+T细胞增殖分化是导致变应性鼻炎（AR）发生的主要生物学事件，TRPV1是新近发现的与CD4+T细胞增殖分化密切相关的通道蛋白。鼻内针刺法为项目组长长期应用临床的创新疗法。前期研究发现其不仅可以改善AR临床症状、调节Th1/Th2平衡、调控中枢参与下的神经源性炎症，可能还存在TRPV1相关的免疫调控途径。我们预初实验发现：鼻内针法可下调TRPV1的表达和活性，改善AR模式动物免疫平衡。鉴此，本项目将以鼻内针刺法通过TRPV1途径对CD4+T细胞增殖分化和免疫因子间的关系，拟以“鼻内针法通过TRPV1途径调控CD4+T细胞活化增殖与分化实现在AR中的抗炎抗敏机制”为聚焦点，进一步系统研究和完善鼻内针法经TRPV1途径实现对AR神经-免疫交互网络的调控及干预机制。本项目的设计分为三部分：（1）通过模式动物观察鼻内针法的干预效果，验证TRPV1在鼻内针法中的作用；（2）制备针刺血清，并通过体内实验1研究鼻内针法（针刺血清）和TRPV1抗体在AR中的抗炎抗敏机制；体内实验2研究鼻内针法（针刺血清）和TRPV1基因敲除在AR中的抗炎抗敏机制；（3）体外实验明晰鼻内针法（针刺血清）对CD4+T细胞活化增殖与分化的影响。. 结论如下：利用模式动物进行鼻内针法干预，行为学观察动物模式动物过敏症状好转，评分降低；鼻黏膜组织病理检查发现鼻内针法对过敏性鼻炎模型动物鼻黏膜具有一定的治疗作用，针刺组动物鼻黏膜细胞紊乱程度较造模动物低；检测鼻黏膜和血清中IgE、TRPV1、神经肽和细胞因子含量变化，发现鼻黏膜SP的表达与血清IgE、IL-4呈正相关，与血清IFN-γ的含量呈负相关。故本研究结果可表明鼻内针刺亦能够通过TRPV1途径降低感觉神经兴奋性，下调SP水平，通过神经免疫系统减少血清IgE及IL-4含量，同时上调IFN-γ含量，进而协调Th1/Th2的失衡状态。另本研究发现TRPV1可促进CD4+T细胞向Tregs细胞增殖分化，进而减缓AR炎性症状。基于此，我们认为鼻内针法可能存在经TRPV1途径调控CD4+T细胞活化增殖与分化实现抗炎抗敏机制。

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