Galectin-3对哮喘豚鼠模型炎性细胞因子和趋化因子的干预作用

Inhibitory Effects of Galectin-3 on the Inflammatory Cytokines and Chemokines in Guinea Pig Asthma Models

目的 观察哮喘豚鼠模型中白细胞介素- 5 (IL - 5 )、Eotaxin和C- C趋化因子受体3(CCR- 3)在嗜酸粒细胞炎症中的表达和Galectin- 3的干预作用。方法 32只豚鼠随机分为正常对照组、哮喘组、Galectin- 3干预组和地塞米松(DXM)干预组。卵蛋白(OVA)致敏和激发制作哮喘模型,Galectin- 3干预组和DXM干预组分别于致敏后第14～16 d激发前1h腹腔注射Galectin- 3(0 .5 m g/ kg)和DXM(1mg/ kg) ,每日1次。观察血、骨髓涂片,肺组织切片细胞总数和嗜酸粒细胞(EOS)比例。肺组织切片用IL - 5、CCR- 3及Eotaxin多克隆抗体染色,光镜下分别计数阳性细胞比例。结果 与正常对照组相比较,哮喘组豚鼠外周血、骨髓、肺组织中EOS计数显著增加(P<0 .0 5 ) ,肺组织中IL- 5、CCR- 3和Eotaxin阳性细胞比例显著升高(P<0 .0 5 ) ,DXM干预后EOS计数、IL- 5、CCR- 3和Eotaxin阳性细胞比例显著降低(P<0 .0 5 ) ,Galectin- 3干预对EOS计数和IL - 5阳性细胞比例的影响与DXM组相当(P>0 .0 5 ) ;Galectin- 3也可下调CCR- 3阳性细胞的表达(P<0 .0 5 ) ,作用弱于DXM(P<0 .0 5 ) ;但Galectin- 3对Eotaxin水平无显著影响(P>0 .0 5 )。结论 哮喘动物模型肺内IL - 5、Eotaxin及其受体CCR- 3表达增强。Galectin- 3可抑制IL -5表达,轻度下调CCR- 3?

Objective To elucidate the roles of interleukin-5 (IL-5),Eotaxin,and CCR-3 in eosinophilic inflammation in guinea pig asthma models and investigate the inhibitory effects of Galectin-3. Methods Thirty-two guinea pigs were randomly assigned to control group,asthma group,Galectin-3 intervention group,and dexamethasone (DXM) intervention group.Asthma models were established by sensitizing-challenging the animals with ovalbumin(OVA).The asthmatic animals were treated with Galectin-3 at 0.5 mg/kg, or DXM at 1 mg/kg,respectively,by peritoneally injection one hour before each aerosol challenge from the 14 th day to 16 th day after sensitization while the control animals were treated with normal saline. The specimens of peripheral blood,bone marrow,and lung tissue on slides were prepared respectively and stained with HE.Then the total number and percentage of eosinophils (EOS) were counted.The lung tissue slide was stained immunochemically with anti-IL-5 polyclonal antibody,anti-Eotaxin polyclonal antibody,and anti-CCR-3 polyclonal antibody,respectively.The immunoactive cells were counted and represented as percentages in total cells. Results The amounts of EOS in peripheral blood,bone marrow,and lung tissue as well as percentages of IL-5,Eotaxin,and CCR-3 immunoactive cells in the lung tissue from asthma group were increased significantly, compared to those from control group.DXM significantly decreased the amounts of EOS,percentages of IL-5,Eotaxin,and CCR-3 immunoactive cells (P<0.05).Galectin-3 had an equivalent suppressive effects on the amounts of EOS and IL-5+ cells with DXM (P>0.05) and down-regulated CCR-3 expression (P<0.05) to a less extent when compared to DXM (P<0.05),but had minimal effect on Eotaxin expression (P>0.05). Conclusion This study provides further evidence for an eosinophil recruitment from bone marrow to circulation blood to lung in asthmatic response,in which over-expression of IL-5,Eotaxin,and CCR-3 could be involved.Galectin-3,a selective inhibitor of IL-5 mRNA transcription,might potentially suppress eosinophilc inflammation and be a compromising specific anti-asthma reagent.