TIM-1对卵蛋白致敏小鼠肺组织黏蛋白5AC及T-bet表达的影响

Effect of T cell Ig and mucin-1 on expression of mucin 5AC and T-bet in lung tissue of asthmatic mice sensitized by ovalbumin

目的研究T细胞免疫球蛋白-黏蛋白1(T cell Ig and mucin-1,TIM-1)对支气管哮喘(简称哮喘)小鼠肺组织黏蛋白(mucin5AC,MUC5AC)及T-bet表达的影响,探讨TIM-1参与气道黏液高分泌的机制。方法卵蛋白(ovalbumin,OVA)腹腔注射致敏小鼠,随机分为正常对照组、哮喘组和哮喘+TIM-1抗体处理组(TIM-1组),每组10只。检测小鼠外周血单个核细胞(PBMCs)TIM-1+细胞比例,实时RT-PCR检测小鼠肺组织MUC5AC mRNA及T-bet mRNA表达变化。结果①哮喘组及TIM-1组小鼠外周血PBMCs中TIM-1+细胞比例分别为(13.15%和7.42%),均高于正常对照组(1.12%)(P<0.01),且TIM-1组低于哮喘组(P<0.01);②与对照组小鼠肺组织表达MUC5AC mRNA(0.223±0.017)相比,哮喘组(1.121±0.082)及TIM-1组(0.771±0.040)表达明显增多(P<0.01),且TIM-1组小鼠肺组织表达MUC5AC mRNA较哮喘组降低(P<0.01);③哮喘组及TIM-1组小鼠肺组织表达T-bet mRNA分别为(0.187±0.011)及(0.689±0.057),较对照组降低(1.001±0.085)(P<0.01),而与哮喘组相比,TIM-1组表达有所增多(P<0.01);④TIM-1+细胞比例与MUC5AC mRNA表达比例呈正相关(r1=0.918,P<0.01),而与T-bet mRNA表达呈负相关(r2=-0.958,P<0.01)。结论抑制TIM-1表达可通过增强T-bet mRNA表达,减少气道MUC5AC mRNA表达,调控气道黏液分泌。

Objective To investigate the effect of T cell Ig and mucin-1 （TIM-l） on mucin5AC （MUC5AC） and T-bet expression in lung tissue of asthmatic mice sensitized by ovalbumin, so as to understand the mechanism of airway mucus hypersecretion. Methods Prepared healthy female mice were randomly divided into control group, asthmatic group and TIM-lmAb treated group, with ten mice in each group. The proportion of TIM-1 positive cells in peripheral blood mononuclear cells （PBMCs）, MUCSAC mRNA and T-bet mRNA expression in lung tissues were detected in three groups. Results （1） The proportion of PBMCs TIM-1 positive cells in asthmatic （13.15%） and TIM-lmAb treated （7.42%） mice were significantly higher than that in the control mice （1.12%）（ P 〈0.01）. That in TIM-lmAb treated mice was lower than that in the asthmatic mice （ P 〈0.01）. （2）MUCSAC mRNA expression in the asthmatic （1. 121±0. 082） and TIM-lmAb treated mice ＇（0. 771±0. 040） were significantly higher than that in the control mice （0. 223±0. 017）（ P 〈0.01）, and that in TIM-lmAh treated mice was lower than that in the asthmatic mice（ P 〈0.01）. （3） T-bet mRNA expression in asthmatic group （0. 187 ±0. 011） and TIM-lmAb treated group（0. 689 ± 0. 057） were significantly lower than that in the control group（1. 001±0. 085）（ P d0.01）, and that in TIM-lmAb treated mice was higher than that in the asthmatic mice（ P 〈0.01）. （4）MUC5AC mRNA expression was positively correlated with TIM-1 positive cells in asthmatic mice（ r1 =0. 918, P d0.01）. However, it was negative relationship between TIM-1 positive cells and T-bet mRNA expression（ r2 = --0. 958, P d0.01）. Conclusions The reduced TIM-1 expression, which decreased the secretion of MUC5AC, even enhanced the T-bet expression, can play a role in reducing mucus hypersecretion and treating asthma.