T细胞免疫球蛋白-黏蛋白-1对卵蛋白致敏小鼠气道MUC5AC及Th1/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）对卵蛋白（OVA）致敏小鼠气道MUC5AC及Th1/Th2细胞因子表达的影响,探讨气道黏液高分泌的机制.方法 OVA腹腔注射致敏小鼠,随机分组为：正常对照组（A组）、哮喘组（B组）和哮喘＋ TIM-1抗体处理组（C组）,每组8只,酶联免疫吸附试验（ELISA）检测小鼠肺泡灌洗液（BALD中IL-4、IFN-γ的水平变化,实时RT-PCR检测外周血单个核细胞（PBMCs） TIM-1 mRNA及气道MUC5AC mRNA表达.结果 （1）与A组小鼠外周血PBMCs表达TIM-1 mRNA（0.618±0.043）相比,B组（1.129±1.101）及C组（0.898±0.071）TIM-1 mRNA表达明显增多（P＜0.01）,且C组明显低于B组（P＜0.01）；（2）B组和C组小鼠BALF中IL-4表达分别为（67.123±3.341） ng/L和（44.217±2.201）ng/L,较A组（23.211±2.142） ng/L]明显增多（P＜0.01）,且C组明显低于B组（P＜0.01）；B组及C组小鼠BALF表达IFN1分别为（53.475±4.776） ng/L和（87.116±5.611）ng/L,均低于A组（124.624±9.292） ng/L] （P ＜0.01）,而C组与B组相比,有所增加（P＜0.01）；（3）B组（1.004±0.081）及C组（0.673±0.029）小鼠气道MUC5A mRNA表达与A组（0.314±0.027）相比,明显增加（P＜0.01）,且C组低于B组（P＜0.01）；（4）小鼠外周血PBMCs TIM-1 mRNA表达与IL-4、MUC5AC表达呈正相关,而与IFN-γ表达呈负相关.结论 抑制TIM-1表达可减少IL-4和MUC5AC的分泌,提高IFN-γ表达,提示在调节黏液高分泌及哮喘治疗中具有意义.

Effect of T cell Ig and mucin-1 on expression of MUC5AC and Thl/Th2 cytokines in airway of asthmatic mice sensitized by ovalbumin

Objective To investigate the effect of T cell Ig and mucin-1 （TIM-1） on MUC5AC and Th1/Th2 cytokines expression in airway 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 （A group）,asthma（B group）and TIM-1mAb（C group）treated groups,with eight mice in each group.The expression of TIM-1 mRNA in peripheral blood mononuclear cells（PBMCs）,MUC5AC mRNA in lung tissues,IL-4 and IFN-γ in bronchoalveolar lavage fluid（BALF） were detected.Results （1） The expression of PBMCs TIM-1 mRNA in B （1.129 ± 1.101）and C groups（0.898 ± 0.071）were significantly higher than that in A group（0.618 ± 0.043）,and that in C group was lower than that in B group （P 〈 0.01）.（2） The BALF levels of IL-4 in B （67.123 ± 3.341） ng/L] and C groups（44.217 ± 2.201）ng/L] were significantly higher than that in A group（23.211 ± 2.142）ng/L],and that in C group was lower than that in B group（P 〈0.01）.Compared with that in A group（124.624 ±9.292）ng/L],IFN-γexpression in B （53.475 ± 4.776） ng/L] and C groups （87.116 ± 5.611） ng/L] were significantly higher.Meanwhile,IFN-γexpression in C gorup was higher than that in B group（P 〈0.01）.（3） MUC5AC mRNA expression in the airway mucous cells in the B （1.004 ± 0.081） and C groups （0.673 ± 0.029） were significantly higher than that in A group（0.314 ± 0.027）.（4）MUC5AC mRNA and IL-4 expression was positively correlated with the expression of TIM-1 mRNA in PBMCs.However,it was negative between TIM-1 mRNA and IFN-γ expression.Conclusions The reduced TIM-1 gene expression,which decreased the secretion of IL-4 and MUC5AC,even enhanced the IFN-γexpression,can play a role in reducing mucus hypersecretion and treating asthma.