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研究异丁司特(ibudilast)对哮喘豚鼠气道嗜酸性粒细胞(eosinophil,EOS)凋亡的作用及其机制。采用卵白蛋白致敏法制备豚鼠哮喘模型。收集支气管肺泡灌洗液(BALF)并进行白细胞计数及分类计数,TUNEL技术原位检测EOS凋亡,RT-PCR技术检测EOS的Fas mRNA表达,酶联免疫吸附(ELISA)法测定BALF中粒细胞-巨噬细胞刺激因子(GM-CSF)及白介素-5(IL-5)的含量。结果表明,异丁司特可明显减少哮喘豚鼠的白细胞总数和EOS数目;在异丁司特剂量组,EOS凋亡细胞明显增多,Fas mRNA的表达显著增强,BALF中GM-CSF、IL-5含量显著降低,与模型组比较有显著性差异。因此,异丁司特抑制哮喘豚鼠气道EOS数目的增加、诱导EOS凋亡、增强Fas mRNA的表达、降低GM-CSF、IL-5含量可能是其拮抗哮喘的重要机制。
To study the effect and mechanism of ibudilast on the apoptosis of eosinophil (EOS) in asthmatic guinea pigs. Guinea pig asthma model was prepared by ovalbumin sensitization. The bronchoalveolar lavage fluid (BALF) was collected and counted for leukocyte count. The apoptosis of EOS was detected by TUNEL technique in situ. The expression of Fas mRNA in EOS was detected by RT-PCR. The expression of granulocytes in BALF was detected by enzyme-linked immunosorbent assay (ELISA) - macrophage stimulating factor (GM-CSF) and interleukin-5 (IL-5) content. The results showed that ibudilast significantly reduced the total number of white blood cells and EOS in asthmatic guinea pigs. In the ibudilast dose group, the number of apoptotic EOS cells was significantly increased and the expression of Fas mRNA was significantly increased. The expressions of GM-CSF and IL-5 Content was significantly lower, compared with the model group there was a significant difference. Therefore, the inhibition of ibudilast on the airway EOS, the induction of EOS apoptosis, the increase of Fas mRNA expression and the decrease of GM-CSF and IL-5 levels in asthmatic guinea pigs may be one of the important mechanisms by which ibudilast may antagonize asthma.