血栓素A2在抗原引起气道嗜酸性粒细胞浸润中的作用

The Role of Thromboxane A2 in Antigen-induced Eosinophil Infiltration into the Airways

关键词:  血栓素  哮喘  嗜酸性粒细胞  趋化因子  动物实验

Key words:  thromboxane  asthma  eosinophil  chemotactic factor  animal experiment

摘要:

为观察血栓素A₂(TXA₂)合成酶抑制剂OKY-046及TXA₂受体拮抗剂S-1452对嗜酸性粒细胞(EOS)浸润气道的影响,探讨TXA₂在EOS浸润过程的作用,应用鸡卵白蛋白(OVA)致敏和反复雾化吸入刺激小鼠以复制过敏性气道炎症模型。除对照组外,各实验组小鼠于每天OVA刺激前分别给予不同剂量OKY-046或S-1452腹腔注射,计数支气管肺泡灌洗液(BALF)中EOS数量并测定BALF中TXB₂和6-酮-前列腺素F_1α(6-Keto-PGF_1α)水平。结果,致敏小鼠给予OVA刺激后BALF中EOS数,TXB₂和6-Keto-PGF_1α水平均显著升高,当以OKY-046或S-1452处理后,BALF中的EOS明显减小,并呈剂量相关性,而且OKY-046尚能引起TXB₂水平呈剂量相关性降低。表明,TXA₂对于EOS浸润到呼吸道具有明显的趋化作用,其合成酶抑制剂或受体拮抗剂对于临床治疗哮喘者可能会具有重要的价值。

Abstract:

To investigate the effects of a thromboxane(TX) A₂ synthetase inhibitor OKY-046 and TXA₂ receptor antagonist S-1452 on antigen-induced eosinophil infiltration into the airways,and study the role of TXA₂ in this infiltration process, the BALB/c mouse model of asthma was established by immunizing and then challenging the animals with 5% ovalbumin(OVA) repeatedly.The experimental groups were treated with different doses of OKY-046 or S-1452 respectively before OVA treatment,except the normal control groups. The numbers of eosinophil in bronchoalveolar lavage fliud(BALF) from each group were counted, and the concentrations of TXB₂ and 6 Keto PGF_1α were detected.The numbers of eosinophil and the concentrations of TXB₂ and 6 Keto PGF_1α in BALF of asthma groups were increased significantly in mice pretreated with OKY-046 or S-1452,producing a dose related decrease in eosinophil numbers,and in mice retreated with OKY-046,also producing a dose related decrease in TXB₂ concentrtions.It suggests that thromboxane A₂ is chemotactic to which the eosinophils infiltrate into the airways.Thromboxane synthetase inhibitor and thromboxane receptor antagonist will be of great value in treatment of asthmatics.