【作者】 张杨；

【导师】 甄宏韬；

【作者基本信息】 华中科技大学 ， 耳鼻咽喉头颈外科， 2012， 硕士

【摘要】 背景：变应性鼻炎是由IgE介导的超敏反应。它是由于鼻粘膜对某些刺激因子过度敏感而产生超出生理范围的鼻粘膜炎症反应。地昔帕明属于三环类抗抑郁药，同时有报道指出它对酸性鞘磷脂酶具有抑制作用。酸性鞘磷脂酶在炎症反应过程中发挥着必不可少的作用。地昔帕明对变应性鼻炎小鼠的作用效果尚未有相关的报道。因此，本实验的研究目的为，抗抑郁药地昔帕明对变应性鼻炎小鼠的鼻部症状是否疗效。方法：雄性BALB/C小鼠用卵清蛋白和氢氧化铝混合液腹腔注射致敏，激发阶段用卵清蛋白滴鼻。变应性鼻炎模型造模成功后，每次卵清蛋白滴鼻后，地昔帕明灌胃。观察变应性鼻炎小鼠的行为学，包括喷嚏和抓鼻次数，来判患病小鼠的严重程度。通过ELISA的方法检测血清卵清蛋白特异性IgE及鼻腔灌洗液中细胞因子IL-4和INF-γ的水平。并且应用流式细胞仪来检测小鼠脾细胞中调节性T细胞和Th17细胞来探讨相关的作用机制。结果：反复用地昔帕明灌胃可以减轻受激发小鼠过敏症状（喷嚏及抓鼻次数）的发生，并且与地昔帕明的计量呈相关性。它还可以减少血清中卵清蛋白特异性IgE的水平和鼻腔灌洗液中IL-4的水平。尽管如此，地昔帕明对鼻腔灌洗液中INF-γ的水平没有明显的作用。此外，地昔帕明还可以通过对Treg细胞和Th17细胞进行调节来削弱变应性鼻炎的气道炎症反应。结论：地昔帕明可以通过抑制产生血清卵清蛋白特异性IgE及IL-4，并且调节脾细胞中CD4+CD25+Foxp3+T细胞和CD4+Th17细胞的比例来发挥其抗过敏的功效。在变应性鼻炎的发病机制中，除已知的Th1/Th2平衡外，还存在Treg/Th17平衡，这为我们研究变应性鼻炎免疫学机制提供了一条新的理论依据，为以后变应性鼻炎的治疗提供了新思路。更多还原

【Abstract】 Background: Desipramine belongs to tricyclic-antidepressant drug and was alsoreported to have an inhibiting activity on acid sphingomyelinas, which wasdemonstrated to play essential roles in inflammation. Allergic rhinitis (AR) is causedby IgE-mediated immediate hypersensitivity and ultimately progresses as chronicnasal inflammation. The present study was designed to investigate whetherdesipramine has treatment effects on nasal symptoms of allergic rhinitis model inmice.Materials and Methods: BALB/C mice were sensitized by intraperitoneal injectionof ovalbumin (OVA) and aluminium hydroxide hydrate gel (alum), followed byrepeated challenge with OVA intranasally. Desipramine was administered orally aftereach instillation of OVA. The multiple aspects (sneezing, scraching etc.) of allergicresponses were evaluated to determine the severity of the mice’s sickness. SerumOVA-specific immunoglobulin E (IgE) levels and interleukin4(IL-4), INF-γ, in nasallavage fluid were measured by ELISA kits respectively to determine theallergy-related cytokines. The numbers of regulated T cells (Treg) and IL-17cells(Th17) were counted by flow cytometry analysis to investigate the mechanisminvolved.Results: Repeated oral administration of desipramine attenuated the progression ofnasal symptoms—sneezing and nasal rubbing in sensitized mice in a dose-dependentmanner. It also suppressed serum OVA-specific immunoglobulin E (IgE) levels andinterleukin4(IL-4) in nasal lavage fluid; however, it had no effect on INF-γ levels inlavage fluid. Moreover, desipramine treatment inhibited the airway inflammation ofallergic rhinitis by regulating the balance between Treg and Th17.Conclusion: These results demonstrate that desipramine has the characteristic ofanti-allergic effect by reducing OVA-specific IgE and IL-4levels, and moduating theratio of spleen CD4+CD25+Foxp3+cell and CD4+IL-17+cells. Basides the theory of Th1/Th2equilibrum, the balance of Treg/Th17can also play a role in the pathogenesisof allergic rhinitis, which provide a new theoretical foundation for the further study.Therefore, desipramine should have potential in the development of therapies forallergic rhinitis.更多还原