YKL-40在哮喘小鼠外周血、肺泡灌洗液、气道上皮中的表达及其与气道嗜酸性粒细胞炎症的关系

Expression and Significance of YKL-40 in Peripheral Blood,Bronchial Alveolar Lavage Fluid and Bronchial Epithelium of Mice Asthma Model

目的:探讨YKL-40在哮喘小鼠外周血、肺泡灌洗液以及气道上皮中的表达及其与气道嗜酸性粒细胞炎症的关系。方法:以卵白蛋白(OVA)致敏并激发建立BALB/C小鼠哮喘模型,对照组以同等剂量的生理盐水代替OVA。造模成功后留取小鼠外周血、肺泡灌洗液、肺组织,HE染色观察肺组织嗜酸性粒细胞浸润情况,免疫组化法观察气道上皮YKL-40的表达,ELISA法定量检测外周血、肺泡灌洗液中YKL-40浓度。结果:(1)哮喘组气道周围有明显的嗜酸性粒细胞浸润,气道上皮杯状细胞增生肥大,并有大量黏液分泌。对照组气道未见明显炎症细胞浸润及粘液高分泌。(2)哮喘组外周血和BALF中YKL-40均明显高于对照组(P<0.05),差异有统计学意义。哮喘组外周血和BALF中Eos数均明显高于对照组(P<0.05),差异有统计学意义。(3)哮喘组气道上皮细胞胞浆中可见YKL-40表达,而对照组未见明显YKL-40表达。结论:(1)哮喘组小鼠外周血、肺泡灌洗液中YKL-40的表达均高于对照组,提示YKL-40可以作为哮喘诊断指标之一。(2)肺泡灌洗液中YKL-40浓度明显高于血液YKL-40浓度,结合免疫组化气道上皮YKL-40的表达,提示哮喘状态下YKL-40主要来源于气道上皮。(3)YKL-40表达水平与Eos数变化趋势一致,提示YKL-40水平可在一定程度上反映气道嗜酸性粒细胞炎症情况。

Objective：To investigate the expression and significance of YKL-40 in peripheral blood, bronchial alveo- lar lavage fluid and bronchial epithelium of mice asthma model. Methods：40 BALB/C mice were involved in the asthma group and the control group. ELISA was used to quantify YKL-40 levels in peripheral blood and Bronchial Alveolar Lavage Fluid. Immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the long. Results：Histological slides showed the extreme peribronchial and perivascular inflammation in mouse model of asthma. Eosinophils cells infiltrated in airway, epithelium detached from the basilar membrane and the narrowed airway lumens were observed in the asthma group. Mucus metaplasia was evaluated with PAS staining, mucous hypersecretion was also observed in the asthma group. YKL-40 levels in peripheral blood and in BALF were significantly elevated in mice with asthma as compared with controls. The levels of peripheral blood YKL-40 in the asthma group were significantly higher than those in the control group. The levels of BALF YKL-40 in the asthma group were also significantly higher than those in the control group. The number of YKL-40 positive cells of bronchial epithelium and subepithelium in lung tissues was counted. There were few YKL-40 expressing cells in the controls, with significantly increased numbers in mice with asthma. Conclusions：Compared with the control group, the concentration of YKL-40 in peripheral blood and BALF of asthma models were both found to be present at elevated levels and there was significant difference between the asthma model and the control group, suggesting that YKL-40 may be used as one of the new biomarkers in asthma diagnosis. BALF concentration of YKL-40 was higher than that in peripheral blood, which suggested that the YKL-40 in asthma mice was mainly from the bronchial epithelium. There was a positive relation between YKL-40 and the eosinophils infiltrat- ed in airway, suggesting that YKL-40 maybe reflect the airway inflammation of eosinophils.