变应性鼻炎区域淋巴结内注射变应原特异性免疫治疗的研究

Allergic rhinitis(AR) is the global health problem . It affects the life quality including social life, sleep, school, and work. Nowadys the treatment regimen were medicine and allergen-specific immunotherapy. Though nasal corticosteroids and antihistamine drugs could control symptoms, but it can't change the natural progression. Standardized allergen-specific immunotherapy is the only way to change the natural progression, prevent to new sensitizations, and reduces risk from AR to asthma. But SLIT was questioned by its safety and long term course. Regional lymph nodes were known as the hub of the local immune regulation, we focus on lymph node injection for allergen-specific immuntherapy.Intralymphatic allergen-special immunotherapy can direct stimulate dendritic cells in lymph nodes, activate the difierentiation from T cells toward Th1 cell, and induced Treg cells expression, enhance IL - 2, IFN - gama, IL - 4 and IL - 10 secretion, and then achieve immune tolerance. We use ovalbumin(OVA) animal model cervical lymph node injection, inducing Treg cells and Foxp3 stable expression in order to investigate injecting the allergen to neck regional lymph node. We try to investigate the immune mechanism and potential clinical feasibility of the new treatment for allergic rhinitis, focusing on those that might have potential clinical therapeutic role in AR.

变应性鼻炎作为全球性健康问题，严重的影响人类健康和社会生活，目前治疗方法主要为药物治疗和特异性免疫治疗。鼻用糖皮质激素和抗组胺等药物虽较好的控制了AR症状，但不能改变自然病程；标准化变应原免疫治疗提高了AR的治疗水平，但疗程长，依从性差，且安全性存在争议。由于颈部淋巴结作为调控局部免疫应答的枢纽，本研究拟采用变应性鼻炎小鼠模型在超声微探头引导下颈部淋巴结内注射变应原直接刺激淋巴结内树突状细胞，激活T细胞朝向Th1分化，并诱导Treg细胞，增强 IL-2、IFN-gama、IL-4和IL-10的分泌，继而达到免疫耐受的目的。拟通过诱导致敏动物体内Treg细胞及Foxp3稳定表达以探讨变应原颈部区域淋巴结注射在免疫治疗中的作用和潜在的临床可行性，为变应性鼻炎的免疫治疗建立新的途径和方法。

本研究采用变应性鼻炎鼠模型免疫治疗及激素治疗疗效对比，变应性鼻炎鼠模型在超声微探头引导下颈部淋巴结内注射变应原直接刺激淋巴结内树突状细胞，激活T细胞朝向Th1分化，并诱导Treg细胞，增强IL-2、IFN-γ、IL-4和IL-10的分泌，继而达到免疫耐受的目的。本研究主要通过诱导致敏动物体内Treg细胞及Foxp3稳定表达，证明变应原颈部区域淋巴结注射在免疫治疗中的作用和潜在的临床可行性，为变应性鼻炎的免疫治疗建立新的途径和方法。首先制备鼻高反应性鼻炎动物模型,评价糠酸氟替卡松对鼻高反应性鼻炎鼻部临床症状的疗效,探讨糠酸氟替卡松对鼻粘膜组织及血清中嗜酸性粒细胞阳离子蛋白(ECP),肥大细胞类胰蛋白酶(MCT)表达水平的影响。结果糠酸氟替卡松能有效的改善动物高反应性鼻炎动物的鼻部症状,同时能有效的降低鼻高反应性鼻炎豚鼠鼻粘膜组织中ECP, MCT的含量.然后分别探讨了颈部淋巴结及腹股沟皮下注射法免疫治疗变应性豚鼠的可行性及免疫耐受情况。结果治疗前模型组和治疗组AR症状评分均大于 5,治疗后A治疗组AR症状评分小于5。治疗组IFN-γ与IL-4 比值较A模型组明显升高,差异具有显著性意义(P<0.05), B治疗组IFN-γ与IL-4比值与B模型组比较,差异无显著性(P>0.05)。 结论:腹股沟淋巴结皮下注射免疫治疗鼠变应性鼻炎效果好,周期短,操作简单,可行性好,是特异性免疫治疗小鼠变应性鼻炎的一种新方法。