摘要
目的:通过对大鼠哮喘模型嗜酸性粒细胞(EOS)上DP1/CRTH2受体及细胞因子变化的分析,研究DP1/CRTH2拮抗剂对大鼠哮喘模型气道炎症的影响和机制。方法:40只雄性SD清洁级大鼠,随机分为正常对照组、哮喘组、CRTH2拮抗剂BAYu3405应用组、DP1受体拮抗剂BWA868C应用组,每组10只。用卵白蛋白(OVA)雾化诱喘。放射配体分析其外周血EOS上的PGD2受体;ELISA测定大鼠血中IL-4和IL-5及IFN-γ水平;肺组织病理切片,HE染色镜检。结果:CRTH2拮抗剂BAYu3405应用组大鼠支气管壁EOS浸润显著减少,血清IFN-γ水平显著增高,IL-4、IL-5水平显著低于哮喘组和DP1受体拮抗剂BWA868C应用组(P<0.01);在肺泡灌洗液中EOS计数较哮喘组和DP1受体拮抗剂BWA868C应用组显著减少(P<0.01),外周血EOS计数与哮喘组和DP1受体拮抗剂BWA868C应用组相似,较正常对照组显著增加(P<0.01)。与正常对照组相比,哮喘组、CRTH2拮抗剂BAYu3405应用组和DP1受体拮抗剂BWA868C应用组外周血EOS上DP总结合和CRTH2受体结合容量显著增加(P<0.01),DP1无显著性差异(P>0.05)。结论:CRTH2受体(DP2)拮抗剂能缓解大鼠哮喘模型气道炎症,减少气道中EOS浸润,可能与CRTH2受体拮抗剂能通过拮抗EOS上增高的CRTH2结合容量,降低IL-4、IL-5和增高IFN-γ水平有关,DP1拮抗剂BWA868C对大鼠哮喘模型气道炎症无显著改善作用。
Objective： To investigate the effect of prostaglandin D2 receptor antagonists on the airway inflammation in rats with asthma.Methods： Forty male SD rats were randomly divided into four groups：Group A（normal control）,Group B（asthma group）,Group C（CRTH2 antagonist BAYu3405 treatment group）,Group D（DP1 antagonist BWA868C treatment group）.Asthma was induced by ovalbumin（OVA） challenge.The rats in each group were sacrificed 24 h after the last challenge of OVA.DP1/CRTH2 receptors on eosinophils（EOS） were measured by radiological binding assay（RBA）.The left lungs were used for histological examinations and bronchoalveolar lavage fluid（BALF） was collected from the right lungs.The total cell numbers,EOS Absolute count and differential cell counts in BALF were performed.Serum concentrations of IL-4,5 and IFN-γ were measured by ELISA.Results： Rats in BAYu3405 treatment group showed profoundly decreased infiltrates of EOS and lymphocytes in the wall of bronchus when compared with those of asthma group and BWA868C treatment group.Serum concentrations of IFN-γ in rats of BAYu3405 treatment group increased,but IL-4 and IL-5 decreased significantly when compared with those in rats of asthma group and BWA868C treatment group（P0.01）,and BALF EOS count was decreased significantly（P0.01）.Peripheral blood EOS count was higher than that in rats of normal control group,but was not significantly different from that in rats of asthma group and BWA868C treatment group.The combining capacity of CRTH2 and DP total combining capacity on EOS in asthma group,BAYu3405 treatment group and BWA868C treatment group were significantly higher than those in Group A（P0.01）.There was no significant difference in DP1 among all the groups（P0.05）.Conclusion： CRTH2,but not DP1 antagonist can effectively ameliorate airway inflammation in rats with asthma.
出处
《浙江大学学报（医学版）》
CAS
CSCD
北大核心
2010年第1期64-70,共7页
Journal of Zhejiang University(Medical Sciences)
基金
浙江省科技厅立项课题基金资助项目(2006C33069)
