基质细胞衍生因子-1/CXC趋化因子受体4在支气管哮喘大鼠气道炎症及气道重塑中的作用

The role of SDF-1/CXCR4 on airway inflammation and airway remodeling in a rat asthma model

目的 探讨基质细胞衍生因子-1（SDF-1）、CXC趋化因子受体4（CXCR4）在支气管哮喘（哮喘）大鼠气道炎症及气道重塑中的作用.方法 将18只SPF级SD雌性大鼠按随机数字表法随机分为对照组、哮喘4周组和哮喘8周组,每组6只.卵清白蛋白（OVA）致敏后,雾化吸人OVA制作哮喘模型.哮喘模型成功后,测定气道压力;通过HE染色、Image-Pro Plus图像分析软件分析大鼠气道平滑肌的嗜酸粒细胞浸润情况,测定支气管管腔的内周长、管壁面积、支气管平滑肌面积以及平滑肌细胞核数;RT-PCR、Western blot方法检测各组大鼠肺组织SDF-1、CXCR4的表达变化;免疫组织化学法检测各组大鼠气道壁SDF-1表达的变化;统计数据并分析SDF-1、CXCR4与哮喘气道重塑及气道炎症的关系.结果 哮喘4周组、哮喘8周组大鼠的气道反应性、气道壁嗜酸粒细胞计数、支气管管壁面积、支气管平滑肌面积、平滑肌细胞核数目均明显高于对照组,哮喘两组间上述指标差异均有统计学意义（均P＜0.01）;RT-PCR检测结果显示,哮喘4周组、哮喘8周组大鼠肺组织SDF-1（分别为0.583±0.004和0.724±0.008）、CXCR4（分别为0.467±0.003和0.655±0.002）的表达明显高于对照组（SDF-1为0.146 ±0.003、CXCR4为0.281±0.002）,哮喘8周组的SDF-1及CXCR4的表达亦明显高于哮喘4周组,差异均有统计学意义Western blot检测结果显示,（均P＜0.01）.Western blot检测结果显示,哮喘4周组、哮喘8周组大鼠气道壁SDF-1的表达（分别为0.270 ±0.006和0.350±0.009）明显高于对照组（0.180±0.009）,哮喘8周组的SDF-1的表达量亦高于哮喘4周组,差异均有统计学意义（均P＜0.01）;各组大鼠肺组织、气道壁SDF-1、CXCR4mRNA及蛋白的表达与气道反应性、嗜酸粒细胞浸润数、支气管壁面积、支气管平滑肌厚度及支气管平滑肌细胞核数均呈正相关（均P＜0.01）.结论 SDF-1/CXCR4信号轴可能在哮喘气道炎症及气道重塑病理过程中起重要作用.

Objective To explore the roles of stromal cell-derived factor 1 （SDF-1） and C-X-C chemokine receptor 4 （CXCR4） on airway inflammation and airway remodeling in rat asthma models.Methods Eighteen female SD rats were randomly divided into 3 groups （n =6）：control group,asthmatic 4 weeks group and asthmatic 8 weeks group.The rats were sensitized and inhaled ovalbumin （OVA）.After the asthma model was successfully established,the airway pressure was measured.The methods of HE staining and Image-Pro Plus image analysis software were used to detect the changes of eosinophils （EOS）,the perimeter of inner bronchial lumen,the wall area,the area of bronchial smooth muscle and the number of smooth muscle cells of airway walls.RT-PCR and Western-blot were used to detect the expression of SDF-1 and CXCR4 in lung tissues among the 3 groups.Immunohistochemistry was used to detect the expression of SDF-1 in airway walls.Results Compared with the control group,the airway responsiveness,the count of EOS,the area of bronchial wall,the area of bronchial smooth muscle,the number of smooth muscle cells of airway walls in the asthmatic 4 weeks and asthmatic 8 weeks were significantly increased,and significant difference between the 2 asthmatic groups was also observed in the above indexes（P ＜ 0.01）.RT-PCR showed that compared with the control group （SDF-1 was 0.146 ± 0.003 and CXCR4 was 0.281 ±0.002）,the expression of SDF-1 （0.583 ±0.004 and 0.724 ±0.008） and CXCR4 （0.467 ± 0.003 and 0.655 ± 0.002） in lung tissues in the asthmatic 4 weeks and asthmatic 8 weeks were significantly increased （P ＜ 0.01）.In addition,compared with the asthmatic 4 weeks group,the expression of SDF-1 and CXCR4 in lung tissues in the 8 weeks asthmatic group were significantly increased （P ＜0.01）.Compared with the control group（0.180 ±0.009）,the expression of SDF-1 in airway walls in the asthmatic 4 weeks and asthmatic 8 weeks groups（0.270 ±0.006 and 0.350 ±0.009） were significantly increased（P ＜ 0.01）.In addition,compared with the asthmatic 4 weeks group,the expression of SDF-1 in airway walls in the 8 weeks asthmatic group was significantly increased（P ＜ 0.01）.The expression of SDF-1 and CXCR4 was correlated positively with the airway responsiveness,the number of EOS,the area of bronchial wall,the area of bronchial smooth muscle and the number of smooth muscle cells of airway walls （P ＜ 0.01）.Conclusions SDF-1/CXCR4 axis may play a key role in airway inflammation and airway remodeling of asthma.