异丁斯特对支气管哮喘豚鼠Th2型细胞因子白介素4、白介素13及嗜酸粒细胞趋化因子的影响

Effect of ibudilast on Th2 type cytokines interleukin-4,interleukin-13 and eotaxin in asthmatic guinea pigs

目的探讨异丁斯特对支气管哮喘(简称哮喘)豚鼠Th2型细胞因子白介素4(interleukin-4,IL-4)、IL-13及嗜酸粒细胞趋化因子(eotaxin)的影响。方法Hartley豚鼠,随机分为正常对照组、哮喘模型组、异丁斯特10、20、30mg/kg组及地塞米松(DXM)给药组。用卵白蛋白致敏制备豚鼠哮喘模型,给药后观察各组肺组织的病理变化;收集支气管肺泡灌洗液(BALF),并对其中的嗜酸粒细胞(eosinophil,EOS)进行计数;采用酶联免疫吸附试验(ELISA)法测定BALF中IL-4、IL-13的含量;双抗体夹心ABC-ELISA法检测eotaxin水平。结果HE染色显示,模型组豚鼠支气管壁及管腔内、血管周围可见大量炎症细胞浸润,平滑肌肥厚,黏膜、肺组织充血水肿,异丁斯特各剂量组及DXM给药组较模型组炎症表现明显减轻;与模型组比较,异丁斯特各剂量组及DXM给药组均能显著降低哮喘豚鼠BALF中EOS的数量;与模型组比较,异丁斯特各剂量组及DXM给药组均能显著降低哮喘豚鼠BALF中IL-4、IL-13含量及eotaxin水平。结论异丁斯特对哮喘豚鼠有治疗作用,其机制可能与降低IL-4、IL-13含量及eotaxin水平,减少气道EOS浸润,从而减轻哮喘气道炎症有关。

Objective To investigate the effect of ibudilast on Th2 type cytokines interleukin-4（IL-4） ,IL-13 and eotaxin in asthmatic guinea pigs. Methods Hartley guinea pigs were randomly divided into control group, bronchial asthma（asthma） group, ibudilast 10,20,30 mg/kg and dexamethasone（DXM） groups. Guinea pig asthma model was established by ovalbumin challenge methods.After therapy, the change of pathology was observed. Then BALF was collected and the number of esosinophil（EOS） was counted. IL-4, IL-13 and eotaxin in BALF were detected respectively by ELISA and ABC-ELISA. Results HE staining showed that there were a large number of inflammatory cells around bronchial wall, the lumen and vessel in model group. Smooth muscle hypertrophy, mucous membrane and lung hyperemia appeared. In contrast,the inflammatory reaction in ibudilast and DXM treated groups was much less. Compared with that of model group,the amount of EOS in BALF remarkably decreased in ibudilast and DXM treated groups. Compared with those of model group, IL-4, IL-13 and eotaxin in BALF obviously decreased in ibudilast and DXM treated groups. Conclusions Ibudilast plays a therapeutic effect in asthmatic guinea pigs,whose mechanism may be explained by the role that ibudilast could decrease IL-4, IL-13 and eotaxin, and reduce EOS infiltration so as to alleviate inflammation.