【作者】 张小琴；

【导师】 岳红梅；

【作者基本信息】 兰州大学 ， 内科学， 2006， 硕士

【摘要】 目的 通过观察地塞米松对大鼠哮喘模型外周血中的M₂受体的自身抗体的影响,探讨M₂受体的自身抗体在哮喘发病中的可能机制。 方法 以卵白蛋白（OVA）致敏法制备Wistar大鼠哮喘模型,分为健康对照组、哮喘模型组和地塞米松组。以细胞外第二环表位肽段的合成肽作为抗原分别通过SA-ELISA检测各组大鼠在1、15、22、29天外周血中的M₂受体的自身抗体;观察各组动物哮喘发作症状、末次OVA攻击24h内支气管肺泡灌洗液及外周血中嗜酸性粒细胞的数量、支气管肺组织病理学改变和气道炎症情况。 结果 哮喘模型组大鼠的哮喘发作症状明显,健康对照组大鼠没有哮喘发作症状,地塞米松组大鼠偶有哮喘发作症状。哮喘模型组与健康对照组相比,气道炎性细胞浸润多,地塞米松组炎症程度轻于哮喘模型组,炎性细胞浸润少。哮喘模型组血中白细胞数及嗜酸性粒细胞数明显高于地塞米松组及健康对照组,差异有统计学意义（P<0.01）。哮喘模型组BALF中总细胞数及嗜酸性粒细胞数明显高于地塞米松组及健康对照组,差异有统计学意义（P<0.01）。在29天哮喘组M₂受体自身抗体阳性率和滴度明显高于地塞米松组和健康对照组,差异有统计学意义（P<0.05）。 结论 在哮喘模型组中M₂受体的自身抗体阳性率和抗体滴度也明显高于健康对照组,提示M₂受体的自身抗体在哮喘的发病中发挥重要的作用;地塞米松组的外周血、BALF中的嗜酸性粒细胞与哮喘组相比有明显减少,地塞米松组的M₂受体的自身抗体阳性率和抗体滴度明显下降,而且肺及气道炎症程度也轻于哮喘组,提示抑制M₂受体的自身抗体的形成可以有效抑制哮喘的发生发展。更多还原

【Abstract】 Objective The present study was to detect autoantibody against M2-muscarinic acetylcholine receptor and investigate the effect of dexamethasone on the autoantibody in asthmatic rats.Methods Thirty-six healthy male wistar rats weighing 180-200g were randomly divided into three groups: normal control group,asthmatic model group, dexamethasone group, with 12 rats in each group. The asthmatic model was established by sensitizing and challenging rats with ovalbulium . The synthetic peptide M₂-muscarinic acetylcholine receptor which corresponded to amino acids sequences of the second extracellular loop of human were used as antigens . Autoantibody against M₂-muscarinic acetylcholine receptor were detected by SA-ELISA on 1st day,15th day,22nd day,29th day.Symptoms of asthmatic attack were observed in three groups. On 29th day ,all rats were killed, eosinophils were counted in the bronchial lavage fluid（BALF）and peripheral blood.then the right lungs were cut to make slides to observe inflammatory changes with microscrop.Results （1） Compared with dexamethasone group and normal control group, symptoms of asthmatic attack were obvious in asthmatic model group.（2） In asthmatic model group, the infiltration of inflammatory cells in lung, peripheral blood and BALF were severe,while it was mild in dexamethasone group. （3）On 29th day ,the rate of positive autoantibody against M₂-muscarinic acetylcholine receptor in the serum from asthmatic model group（66.7%） were significantly higher than that of dexamethasone group（16.7%） and normal control group （8.3%）,respectively.（4）The geometric mean of autoantibodies against M2-muscarinic acetylcholine receptor titer in asthmatic model group and dexamethasone group were 1:105and 1:30, respectively. In dexamethasone group, the rate of positive autoantibody and the titer of autoantibodies in the serum was lower than that of asthmatic model group . Conclusion:1. In asthmatic model group, the rate of positive autoantibody and the titer of autoantibodies against M2-muscarinic acetylcholine receptor in the serum have been kept in a very high level, which indicates that the antibody against M2-muscarinic acetylcholine receptor play a very important role in the pathogenesis of asthma.2. In dexamethasone group,not only the rate of positive autoantibody and the titer of autoantibodies against M2-muscarinic acetylcholine receptor in the serum decreased significantly ,but also the infiltration of inflammatory cells in lung, peripheral blood and BALF reduced significantly .It shows the inhibition of autoantibody against M2.muscarinic acetylcholine receptor can effectively prevent the development of asthma.更多还原