CCR7在烟草烟雾暴露后哮喘大鼠肺部的表达及其对IL-12和气道炎症影响的研究

The role of CCR7 on airway inflammation and IL-12 in asthmatic rats with tobacco smoke exposure

目的探讨CC趋化因子受体(CC chemokine receptor,CCR)7在烟草烟雾暴露加重哮喘肺部炎症中的作用。方法 40只Wistar大鼠随机分为四组:对照组(C组)、哮喘组(A组)、烟雾暴露组(S组)、烟雾暴露+哮喘组(AS组),参照文献建立各组大鼠模型。收集外周血和支气管肺泡灌洗液(Bronchoalveolar lavage fluid,BALF),BALF中白细胞计数及分类采用HE染色,血浆和BALF中IL-12蛋白的检测采用酶联免疫吸附试验法(ELISA),肺部CCR7蛋白的表达采用免疫组织化学法检测。结果 (1)AS组、A组大鼠肺部CCR7表达较C组增加,AS组大鼠肺部CCR7表达较A组增加,差异均有统计学意义(均P<0.01)。(2)AS组、A组大鼠血浆、BALF中IL-12表达较C组降低(均P<0.01);AS组大鼠血浆、BALF中IL-12表达较A组降低(均P<0.05)。(3)A组和AS组大鼠BALF白细胞总数、中性粒细胞、淋巴细胞比例较C组增加,差异均具有统计学意义(均P<0.01);AS组大鼠BALF嗜酸粒细胞较A组减少,白细胞总数、中性粒细胞比例较A组增加,差异均具有统计学意义(均P<0.01)(4)CCR7的表达与血、BALF中IL-12表达呈负相关(分别r=-0.677,r=-0.692,均P<0.01);与BALF中白细胞数量、中性粒细胞数量呈正相关(分别r=0.790,r=0.825,均P<0.01)。结论烟草烟雾暴露可增加哮喘大鼠肺部CCR7的表达,同时影响BALF细胞计数及分类,导致IL-12表达降低,提示CCR7可能在烟雾暴露加重哮喘肺部炎症的机制中发挥一定作用。

Objective To explore the role of CC chemokine receptor（CCR） 7 on tobacco smoke exposure aggravating asthma.Methods 40 rats were randomly divided into the control group（ C）,the asthma group（ A）,the cigarette smoke exposure group（ S）,and the tobacco smoke exposure combined asthma group（ AS）.BALF was assessed for total and differential cell counts.The expression of CCR7 protein was determined by immunohistochemistry,and IL-12 were determined by ELISA.Results（1） Compared with the C group,CCR7 protein increased in the A group and the AS group（ P〈0.01,respectively）.Compared with the A group,CCR7 protein increased in the AS group（ P〈0.01）.（2） Compared with the C group,IL-12 decreased remarkably in the A group and AS group（ P〈0.01,respectively）.Compared with the A group,IL-12 decreased in the AS group（ P〈0.05）.（3） Compared with the C group,numbers of blood leucocytes,percentages of lymphocytes and neutrophil of BALF increased in the A group and the AS group（ P〈0.01）.Compared with the A group,the numbers of blood leucocytes and percentages of neutrophils of BALF increased and eosinophils decreased obviously in the AS group（ P〈0.01）.（4） The expression of CCR7 protein was positively correlated with the numbers of blood leucocytes and neutrophil of BALF and was negatively correlated with IL-12 of peripheral blood and BALF.Conclusion Tobacco smoke exposure can make the expression of CCR7 protein increase,affect the cell count and classification of BALF and lead to IL-12 expression decreased,resulting in further aggravation of asthmatic airway inflammation.