异丁司特对哮喘豚鼠气道嗜酸性粒细胞凋亡的作用及其机制

Effect of ibudilast on apoptosis of airway eosinophil in asthmatic guinea pigs

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。

This study is to investigate the effect of ibudilast on apoptosis of airway eosinophil in asthmatic guinea pigs and its mechanism. Experimental asthma model of guinea pigs was induced with ovalbumin （OVA）. Differential count in BALF was examined. The apoptosis of eosinophils （EOS） was labeled with TdT-mediated dUTP nick end labeling （TUNEL） technique. Fas mRNA expression of EOS was detected by reverse transcriptionpolymerase chain reaction （RT-PCR）. The quantification of GM-CSF and IL-5 in BALF was conducted with ELISA. After treatment of ibudilast, the number of EOS and the quantification of GM-CSF and IL-5 decreased significantly. The number of apoptotic cells as well as Fas mRNA expression of EOS obviously increased. The results indicated that anti-asthma mechanisms of ibudilast can antagonize asthma through decreasing the number of EOS, inducing apoptosis of EOS, enhancing Fas mRNA expression of EOS and reducing the content of GM-CSF and IL-5.