CXCR4在哮喘小鼠肺组织中的表达及氯喹的干预作用

发布时间：2018-04-25 09:38

本文选题：哮喘 + 趋化因子受体CXCR　；参考：《免疫学杂志》2014年11期

【摘要】：目的检测哮喘小鼠中趋化因子受体CXCR4的表达及其拮抗剂氯喹(CQ)的干预作用。方法将6~8周SPF级Balb/c小鼠随机分成对照组、哮喘组和氯喹干预组,哮喘组和氯喹干预组用鸡卵清蛋白(OVA)致敏和激发建立哮喘小鼠模型,干预组于激发前30 min给予CQ,连续3 d,对照组用PBS代替。最后1次激发24 h内小鼠肺功能仪检测小鼠气道高反应;最后1次激发48 h内检测支气管肺泡灌洗液(BALF)中细胞总数及细胞分类计数;HE染色光镜下观察肺组织的病理炎症改变,免疫组化染色检测肺组织CXCR4的表达;荧光定量PCR(Q-PCR)测定肺组织中CXCR4 mRNA的表达。结果哮喘组气道高反应及BALF中细胞总数明显高于对照组,干预组小鼠气道高反应及BALF中细胞总数与哮喘组相比显著降低;BALF中哮喘组嗜酸性粒细胞、中性粒细胞和单核细胞数较空白组显著增加,而氯喹干预组较哮喘组显著减低;HE染色结果显示哮喘组肺部炎症细胞浸润明显,干预组与哮喘组相比明显减轻,病理评分降低;免疫组化显示哮喘组CXCR4在气道上皮细胞呈强阳性表达,干预组表达呈弱阳性;哮喘组CXCR4 mRNA的表达较对照组升高,氯喹干预组较哮喘组CXCR4 mRNA表达量降低;CXCR4表达量与BALF细胞总数呈正相关。结论 CXCR4可能参与哮喘小鼠的气道炎症和气道高反应的发生,氯喹能改善哮喘小鼠的气道高反应和气道炎症可能与拮抗CXCR4相关,为氯喹治疗哮喘提供理论和实验依据,为开发治疗哮喘新药提供新的思路。
[Abstract]:Aim to investigate the expression of chemokine receptor (CXCR4) in asthmatic mice and the intervention of chloroquine. Methods six weeks and eight weeks SPF Balb/c mice were randomly divided into control group, asthma group and chloroquine intervention group, asthma group and chloroquine intervention group were sensitized with chicken ovalbumin (ovalbumin) and stimulated to establish asthma mice model. The intervention group was given CQ 30 min before stimulation for 3 days, while the control group was replaced by PBS. The lung function instrument was used to detect the airway hyperresponsiveness in mice within 24 h after the last challenge, and the total number of cells and cell classification count in BALF (bronchoalveolar lavage fluid) were measured within 48 h after the last stimulation. The pathological inflammation of lung tissue was observed by HE staining under light microscope. The expression of CXCR4 in lung tissue was detected by immunohistochemistry and the expression of CXCR4 mRNA in lung tissue was detected by fluorescence quantitative PCR Q-PCR. Results the airway hyperresponsiveness and the total number of cells in BALF in asthma group were significantly higher than those in control group. The airway hyperresponsiveness and the total number of cells in BALF in intervention group were significantly lower than those in asthma group, and the number of eosinophils in asthma group was significantly lower than that in asthma group. The number of neutrophils and monocytes was significantly increased compared with the control group, while the neutrophil and monocyte count in the chloroquine group was significantly lower than that in the asthmatic group. The results showed that the infiltration of inflammatory cells in the lung was obvious in the asthma group, and the pathological score was lower in the intervention group than in the asthmatic group. Immunohistochemical staining showed that the expression of CXCR4 was strongly positive in airway epithelial cells in asthmatic group and weakly positive in intervention group, and the expression of CXCR4 mRNA in asthma group was higher than that in control group. The expression of CXCR4 mRNA in chloroquine intervention group was significantly lower than that in asthma group. There was a positive correlation between the expression of CXCR4 and the total number of BALF cells. Conclusion CXCR4 may be involved in the development of airway inflammation and airway hyperresponsiveness in asthmatic mice. Chloroquine can improve airway hyperresponsiveness and airway inflammation in asthmatic mice, which may be related to antagonistic CXCR4, which provides theoretical and experimental basis for chloroquine in the treatment of asthma. To provide new ideas for the development of new drugs for the treatment of asthma.
【作者单位】：重庆医科大学儿童发育疾病研究省部共建教育部重点实验室;重庆医科大学附属儿童医院呼吸一、二病房;
【基金】：国家自然科学基金面上项目(81070014) 重庆市卫生局重点项目(2010-1-46)
【分类号】：R562.25

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