大鼠支气管哮喘模型中前列腺素D2水平和嗜酸粒细胞上受体改变研究

Changes of prostaglandin D2 levels and receptor on eosinophil in rat bronchial asthma model

目的前列腺素D2（PGD2）通过嗜酸粒细胞（EOS）上前列腺素受体（DPI／CRTH2）调控其分化、成熟、迁移和募集功能，本研究试网了解在哮喘时外周血PG跳水平和EOS上DPI／CRTH2受体表达改变，探讨哮喘时EOS气道中浸润的机制。方法20只雄性SD清洁级大鼠，随机分为正常对照组、哮喘组，每组10只。用卵白蛋白（OVA）雾化诱喘。用放射配体法分析其外周血EOS上的PGD2受体；用ELISA测定大鼠血中PGD2水平；肺组织病理切片，HE染色镜检。结果与正常对照组相比，哮喘组大鼠支气管壁有显著的淋巴细胞和EOS浸润，具有典型的哮喘病变，哮喘组外周血PGD2水平显著高于正常对照组（P〈0．01），哮喘组外周血和支气管肺泡灌洗液中EOS计数较正常对照组显著增加（P〈0．01）；哮喘组与正常对照组相比外周血EOS上DP总结合和CRTH2受体结合容量显著增加（P〈0．01），DPI差异无统计学意义（P〉0．05）。结论大鼠哮喘模型中外周血PGD2水平增高，同时EOS细胞上CRTH2受体表达增多，增高的PGD2可通过CRTH2信号转导途径，使EOS趋化作用增强，向气道内浸润，产生炎症效应，导致哮喘病理上EOS浸润特征。

Objective Prostaglandin D2 （PGD2） has been shown to have regulating functions of the differentiation, maturation, migration and recruitment on eosinophils （EOS）. This occurs through the interaction of PGD2 with the receptor expressed on EOS. This study attempts to understand the levels of prostaglandins and the change of DP1/CRTH2 receptors on EOS in asthma, to explore the mechanism of the infiltration of EOS in airway. Methods Twenty male SD rats were randomly divided into normal control group（ n= 10）, asthma group （ n = 10）. Asthma was induced by ovalbumin challenge. PGD2 receptor on EOS were measured by radiological binding assay. PGD2 levels in peripheral blood was measured by ELISA. The left lung was used for histological examinations and bronchalveolar lavage fluid （BALF） was collected from the right lung. Results Compared with the normal control group, asthma group had significant infiltration of EOS and lymphocytes in bronchial wall, there was the typical changes of asthma. PGD2 in peripheral blood in asthma group was significantly higher than the normal control group （P 〈 0.01 ）, EOS count in peripheral blood and BALF in normal control group increased significantly （ P〈0.01 ）. DP total binding capacity and CRTH2 binding capacity on EOS in asthma group were significantly higher than the control group （ P 〈0.01）. DP1 was no significant differences （ P 〉 0.05）. Conclusions PGD2 was significantly increased in asthma, and the CRTH2 receptor on EOS increased expression. The increased production of PGD2 EOS will strengthen the role of ehemotaxis, infiltration to the airway,leading to arguments on EOS infiltration characteristics in asthma.