摘要
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、哮喘模型组(哮喘组)和哮喘模型+TIM-1抗体处理组(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水平及黏液细胞数量和细胞体积的改变。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%)均高于正常组(0.64%,P<0.05),且TIM-1抗体组低于哮喘组(P<0.05)。(2)哮喘组及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[(1 681.13±613.55)pg/ml,(513.42±86.87)pg/ml]水平均高于正常组[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。
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
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2012年第6期581-584,共4页
Academic Journal of Second Military Medical University
基金
国家自然科学基金(30670912)
上海市自然科学基金(11ZR1448600)~~
