【作者】 张水娟；

【导师】 陈季强； 谢强敏；

【作者基本信息】 浙江大学 ， 药理学， 2006， 硕士

【摘要】 研究背景 支气管哮喘是一种由多种细胞、细胞因子和炎症介质引起的、以气道高反应为特征的变态反应性炎症性疾病。长期以来,由于脑的特殊的结构,如脑膜,皿脑屏障等,被认为是免疫赦免器官,而对支气管哮喘的认识也局限于外周的局部炎症性慢性疾病。随着研究的深入,发现哮喘是全身性的疾病,中枢神经系统（CNS）也参与了哮喘的病理或生理学改变。因而对哮喘时神经活动的研究不再局限于外周,对脑内的研究也逐渐增多。白三烯和组胺是重要的炎症介质,外周的白三烯和组胺在哮喘中的炎症介质作用已得到了广泛的肯定。白三烯和组胺除了存在于外周参与免疫反应外,也存在于CNS, 参与了脑的许多病理生理反应,发挥了重要的神经免疫调节作用。有资料表明,哮喘大鼠脑内白三烯B₄（LTB₄）含量升高,哮喘豚鼠脑内组胺含量上升,但他们对哮喘有无调节作用,及发挥何种调节作用目前尚未见有文献报道,这是我们在本研究中想探讨的问题。 研究目的 观察白三烯B₄和组胺侧脑室注射对抗原攻击致敏大鼠引起的支气管收缩反应及气道炎症的影响。 研究方法 采用卵白蛋白致敏SD雄性大鼠,在抗原攻击前通过侧脑室对清醒的致敏大鼠注射LTB₄、受体拮抗剂U-75302及组胺,观察其对致敏大鼠在抗原攻击后肺阻力和肺动态顺应性变化的影响。反复抗原攻击致敏大鼠制作致敏大更多还原

【Abstract】 Background Asthma is a chronic inflammatory disease of the airway characterized by airway hyper-responsiveness. It is caused by numerous cells, cytokines and mediators. Brain has traditionally been regarded as an immunologically privileged organ. This viewpoint has been based on the presence of meninges and a tight blood-brain barrier（BBB）. Asthma has been considered as a chronic inflammatory disease in periphery. With the research development to asthma, it has find that asthma is not a "Free-standing event" of "independent organ" in periphery, multiple mechanism including central nervous system （CNS） take part in the pathophysiological changes of asthma. Now more and more researchers pay attention to the relationship between CNS and asthma. Leukotrienes and histamine are important mediators, which not only exist in periphery but also in CNS. Recent researchs show that leukotriene B₄ （LTB₄） content in cerebral cortex and lung tissue are increased in an asthmatic model of rat, and histamine content in cerebral cortex are increased in asthmatic guniea pigs, but to date there still no report about their effect in brain on asthma function. To explore if LTB₄ and histamine present regulatory effects on asthma-like reaction in rats, which help to understand themechanism of asthma, we take this program.Objective To investigate regulation effects of leukotriene B4 and histamine onbronchoconstriction and airway inflammation induced by antigen in an asthmaticmodel of rat.Methods Ovalbumin sensitized and challenged male SD rats were used asasthmatic model. Leukotriene B4, selective BLTi receptor antagonist U-75302 andhistamine were administrated intracerebroventricularly in the asthmatic model of rat,the airway resistance（RL） and dynamic lung compliance（Cdyn） before and afterantigen-challenged were observed. The total white cell and differential cell count inbronchoalveolar lavage fluid（BALF） were performed. Inflammatory cells infiltrationwere determined by lung pathological section.Results 1, Leukotriene B4 and histamine by icv inhibited the increase in Rl and thedecrease in Cdyn induced by antigen challenge. After pretreatment of U-75302intracerebroventricular injection, lung resistance increased and lung compliancedecreased.2> Leukotriene B4 and histamine by icv significantly reduced total white cell and the number of eosinophil and neutrophil. Leukotriene B4 and histamine also inhibited eosinophil infiltration below airway mucosa and around blood vessel. Conclusion 1 ^ Leukotriene B4 by icv inhibit bronchoconstriction and airway inflammation, and its antagonist U-75302 reverse the regulatory effect of leukotriene B4. These results indicate that leukotriene B4 in central nervous system may have negative feedback regulatory effects on asthma-like reaction in rats.2 -, Histamine by icv inhibit bronchoconstriction and airway inflammation, suggesting that the increased histamine in central nervous system may have regulatory effects on asthma-like reaction in rats.更多还原