辛夷挥发油抗过敏性哮喘气道炎症的作用的机理研究

【作者】 李寅超；

【导师】 沈映君；

【作者基本信息】 成都中医药大学 ， 中药药理学， 2004， 博士

【摘要】 辛夷是常用解表药，其性温、味辛，归肺、胃经，具有散风寒、通鼻窍之功效，在鼻科用药中居有重要地位，中医临床广泛用于鼻渊、鼻鼽等的治疗，疗效显著，挥发油是其主要有效成分之一。本课题在导师前期对辛夷挥发油（VOMbP）药效学研究成果及相关文献报道的基础上，结合现代医学对哮喘与鼻渊、鼻鼽发病机制关系的研究进展，提出VOMbP可能具有抗过敏性哮喘气道炎症作用的设想。并采用免疫组织化学、图象分析技术、酶联免疫吸附等现代研究手段，从整体动物、组织器官和细胞分子水平，对VOMbP抗过敏性哮喘气道炎症的作用及其机制进行了较深入、系统的研究。结果显示： 1．VOMbP具有显著的抗过敏性哮喘气道炎症的作用，具体表现在：①可明显延长致敏动物的引喘潜伏期，减轻哮喘早期相反应的症状。②能抑制哮喘动物晚期相血循环和气道嗜酸性粒细胞（EOS）的增加和浸润，拮抗EOS等炎症细胞及其炎症介质对气道粘膜组织的损伤、抑制气道炎症时微血管通透性的增加，减少炎性蛋白的渗出，减轻粘膜充血水肿等。 2．VOMbP抗过敏性哮喘气道炎症的作用机理与以下途径有关： ①VOMbP抑制哮喘早期相主要效应细胞——肥大细胞（MC）在气道的浸润和脱颗粒，稳定MC细胞膜。从哮喘发生的始动环节发挥其抑制效应。②降低哮喘动物血浆中的炎症介质白三烯B₄（LTB₄）的浓度。③通过上调哮喘动物体内γ-IFN⁺表达水平，使处于失衡状态的Th1／Th2趋向恢复。④显著抑制哮喘动物气道重要的“炎前因子”TNF-α过度表达，从而间接阻断EOS等炎细胞与血管内皮的粘附和核因子-κB的生成活化。⑤抑制粘附分子VCAM-1的表达，直接阻止血循环中炎细胞与内皮的粘附。⑥抑制EOS特异性趋化因子Eot在气道炎症部位的过度表达，阻止血循环中EOS向气道炎症部位的趋化募集。⑦抑制气道炎症部位IL-5的过度表达，降低IL-5的水平，进而影响骨髓中EOS的前体细胞的增 成都中医药大学博士学位论文殖、分化，影响成熟活化的EOS向气道粘膜趋化。⑧直接抑制气道炎症反应中心环节核因子一忍的活化，影响炎性介质、细胞因子、粘附分子、炎症相关酶、5一脂氧酶等与炎症反应相关的基因转录和表达，从而控制整个炎症反应。 以上研究结果显示，VON[bP具有显著的抗过敏性哮喘气道炎症的作用。其作用机理是:抑制肥大细胞脱颗粒:上调Y一m旷表达水平;抑制Eos从生成活化、趋化、粘附和在气道粘膜的聚集;降低血中LTB4的含量:抑制气道炎症中核因子一忍的活化。进一步证明VON伪P是抗过敏性哮喘气道炎症的主要物质基础。该研究扩展了辛夷的传统功效，丰富了解表药中辛味挥发油的现代药理内涵，为进一步开发新的非田体类抗哮喘药物，提供了重要的实验依据.更多还原

【Abstract】 Flos Magnoliae is one of commonly used Chinese herb which can relieve Exterior Zheng. It belonging to lung and stomach meridian is warm in nature and pungent in flavor and has the action of expelling Cold and clearing the nasal passage, so it stands important in nose department. Flos Magnoliae has been applied to treating allergic rhinitis and nasosinusitis and has significant effect. Volatile oil is one of its main effective components. This topic is based on the study of pharmacodynamics on the Volatile oil of Magnolia biondii Pamp (VOMbP) performed by my tutor and other studies on mechanism of asthma, rhinitis and nasosinusitis in western medicine and pertinent literatures. In this topic, our suggestion is VOMbP had the effect of anti-inflamation of airway in asthma. Adopted image analysis technique, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and other modem research methods, we studyed the effect of VOMbP on allergic inflammation of airway in asthma and its mechanism from the level of whole animal, organ and cell molecule, our results show as follows:1. VOMbP had the marked effect of anti--inflamation of airway in allergic asthma. Presented in detail below: (1)VOMbP could lengthen the incubation period, relieve and delay the occurance of early phase reaction (EPR) symptoms in sensitization animal. (2) VOMbP could inhibite the increase and infiltration of EOSinophil (EOS) in peripheral blood,and airway in late asthmatic reaction (LAR), resist mucous membrane injury by EOS or other inflammation cells and inflammation media, suppress the microvessel permeability and the bleeding of inflammatory protein and relieve mucous membrane congestion and dropsy caused by airway allergic inflammation.2. The effect of VOMbP on anti- inflammation of airway in allergic asthma was realized maybe through the pathways displayed below: (1) inhibiting the generation of mast cell (MC), the effector cell of EPR in asthma, stabilizing cell membrane ofMC, inhibiting de-particles of MC, thus inhibiting inflammation in the early phase of asthma. (2) decreasing the content of leukotrine B4 (LTB4) produced by lipoxigenase pathway. (3) up-regulating the expression of interferon- (IFN -), regulating the balance of THI/ TH2. (4) preventing the over expression of tumour necrosis factor-a (TNF- ), thereby blocking indirectly the activation of NF-B and adhesiveness of inflammatory cells such as EOS to blood vessel endothelial cells. (5) inhibiting the expression of vascular cell adhesion molecule-1 (VCAM-1) and preventing inflammation cells adhesiving vascular endothelial cells. (6) inhibiting the over expression of Eotaxin, the specific chemokine of EOS. (7) resisting EOS differentiating and activating dependence of cytdkine IL-5. (8)blocking the activation of Nuclear factor- B (NF-B).From the results above, we can see VOMbP had the notable effect of anti-inflamation of airway in allergic asthma which may be through inhibiting de-particles of MC , up-regulating the expression of IFN-, inhibiting the generation and activiation of EOS and chemotaxis and adhesiveness of EOS and other inflammation cells, the two important links of cell recruitment, blocking the activation of NF- B. We also proved VOMbP was the main substance of anti-inflamation of airway in allergic asthma. Maybe this study has expanded the function of Flos Magnoliae in TCM and enriched the content of modern pharmacology on Volatile oil, the substance of pungent in flavor in Chinese herbs relieving Exterior Zheng. Meanwhile this study may present the important experimental evidence for developing a new non-steroid anti-asthma drug.更多还原