TIM-1对哮喘小鼠气道MUC5AC及Th2细胞因子表达的影响

目的 研究T细胞免疫球蛋白-黏蛋白-1(TIM-1)表达对哮喘小鼠气道MUC5AC及Th2细胞因子的作用，探讨气道黏液高分泌的机制。方法 30只健康雌性C57BL/6小鼠，按随机数字表法分为正常组、哮喘组和TIM-1抗体组，每组10只。检测小鼠外周血单个核细胞（PBMCs）TIM-1+细胞比例、气道MUC5AC mRNA表达、肺泡灌洗液（BALF）中IL-13、IL-4、IL-5表达及黏液细胞和细胞内黏液量的改变。结果（1）哮喘组及TIM-1抗体组小鼠外周血PBMCs中TIM-1+ 细胞比例（11.20%，5.11%）均显著高于正常组（0.64%，P<0.05)；而TIM-1抗体组明显低于哮喘组（P<0.05）。（2）哮喘及TIM-1抗体小鼠气道黏液细胞MUC5AC mRNA相对表达(17.3±1.4,5.6±0.3)及IL-13(16.80±0.63) ng/ml，(5.70±0.64)ng/ml]、IL-4（614.72±117.39）pg/ml，（325.78±86.54）pg/ml]、IL-5（1681.13±613.55）pg/ml，（513.42±86.87）pg/ml]表达量均显著高于正常组1, (1.09±0.25)ng/ml，（17.56±3.01）pg/ml，（30.78±9.67）pg/ml ]，TIM-1抗体组小鼠上述指标显著低于哮喘组（P<0.05）。（3）气道MUC5AC及IL-13表达与TIM-1+细胞表达均呈正相关，r1=0.946，P1=0.004; r2=0.984，P2=0.000. 结论 哮喘小鼠外周血TIM-1+细胞升高，可致气道黏液过度分泌；抑制TIM-1表达可减少哮喘气道黏液高分泌。调节TIM-1表达有可能成为减少黏液高分泌及治疗哮喘的新途径。

Effect of T cell Ig and mucin 1 on expression of MUC5AC and Th2 cytokine in airway of asthmatic mice

Objective To investigate the effect of T cell Ig and mucin 1(TIM-1) on MUC5AC and Th2 cytokine expression in the airway of asthmatic mice,so as to understand the mechanism of airway mucus hypersecretion. Methods Thirty healthy female C57BL/6 mice were randomly divided into control,asthmatic and TIM-1 mAb treated groups,with 10 mice in each group.The proportion of TIM-1 positive cells in peripheral blood mononuclear cells(PBMCs),MUC5AC mRNA expression in the airway,levels of IL-13,IL-4 and IL-5 in bronchoalveolar lavage fluid(BALF),and the number and volume of airway mucous cells were examined in the three groups. Results The proportions of PBMCs TIM-1 positive cells in asthmatic(11.20%) and TIM-1 mAb treated(5.11%) mice were significantly higher than that in the control group(0.64%,P<0.05),and that in TIM-1 mAb treated mice was significantly lower than that in the asthmatic mice(P<0.05).(2) MUC5AC mRNA expression in the airway mucous cells in the asthmatic(17.3±1.4) and TIM-1 mAb treated(5.6±0.3) mice were significantly higher than that in control mice(P<0.05).The BALF levels of IL-13(ng/ml),IL-4(pg/ml),and IL-5(pg/ml) were 16.80±0.63,614.72±117.39,and 1 681.13±613.55 in the asthmatic,and were 5.70±0.64,325.78±86.54,and 513.42±86.87 in TIM-1 mAb treated mice,respectively,which were all significantly higher than those in the control mice(1.09±0.25] ng/ml for IL-13,17.56±3.01] pg/ml for IL-4,and 30.78±9.67] pg/ml for IL-5,P<0.05).And all the above parameters in the TIM-1 mAb treated mice were significantly lower than those in the asthmatic mice(P<0.05).(3) MUC5AC and IL-13 expression in the airway was positively correlated with TIM-1 positive cells in asthmatic mice(r1=0.946,P1=0.004;r2=0.984,P2=0.000). Conclusion TIM-1 positive cells are increased in PBMCs in asthmatic mice,which can result in airway mucous cell metaplasia and mucus hypersecretion.Inhibition of TIM-1 expression can reduce mucus hypersecretion.Regulation of TIM-1 might be a novel approach for asthma treatment.