支气管哮喘患者诱导痰中HMGBl和RAGE水平的变化及临床意义

Changes of HMGB1 and RAGE in induced sputum from patients with bronchial asthma

目的探讨HMGBI蛋白和晚期糖基化终产物受体（RAGE）与支气管哮喘发病机制及严重程度的关系。方法按标准纳入急性发作期哮喘患者64例（哮喘组），健康体检者20名（对照组）；哮喘组给予布地奈德与福莫特罗的联合制剂吸入治疗4周。治疗前后分别对各组进行肺功能检测和诱导痰检查，记录第1秒用力呼气容积（FEV，）占预计值的百分比（FEV，％），行诱导痰中中性粒细胞分类计数，酶联免疫吸附法检测诱导痰中HMGBl和RAGE水平。结果治疗前哮喘组诱导痰中中性粒细胞百分比、HMGBl和RAGE水平均高于对照组（均P〈0．01）；重度哮喘者诱导痰中中性粒细胞百分比及HMGBl水平均高于轻度哮喘者（均P〈0．01），但RAGE水平在轻、中、重度哮喘者之间差异无统计学意义（P〉0．05）。治疗后哮喘组诱导痰中中性粒细胞百分比及HMGBl和RAGE水平均低于治疗前（均P〈0．01）；治疗未控制者诱导痰中中性粒细胞百分比、HMGBl和RAGE水平高于完全控制者（均P〈0．05）；哮喘组HMGBl、RAGE均与FEV，％呈负相关（r=-0．830和r=-0．632，均P〈0．01）；诱导痰中HMGBl、RAGE均与中性粒细胞百分比呈正相关（r=0．820和r=0．623，均P〈0．01）；诱导痰中HMGBl水平与RAGE水平呈正相关（r=0．929，P〈0．01）。结论HMGBl和RAGE参与了哮喘的气道炎症过程，HMGBl与哮喘的严重程度相关；诱导痰中HMGBl和RAGE水平可作为观察疗效的参考指标。

Objective To explore the relationship between HMGB1 （high mobility group box-1 ） protein and receptor for advanced glycosylation end products （ RAGE ） and the nosogenesis and severity of bronchial asthma. Methods Based on the criteria, the asthma group included 64 acute-onset asthma patients while the control group had 20 healthy cases. The asthma group received a 4-week combination inhalation therapy of budesonide and formoterol. Lung functions and induced sputum examinations were conducted before and after treatment. The percentage of a second forced expiratory volume in the predicted value （FEV1%） was recorded. A differential count of neutrophilic leukocyte in reduced sputum was performed. And the sputum levels of HMGB1 and RAGE were detected by ELISA （enzyme linked immunosorbent assay）. Results Prior to treatment, the neutrophilic leukocyte percentage and the levels of HMGB1 and RAGE were all higher than those of control group （ P 〈 O. 01 ）. The induced sputum of severe asthma patients had higher levels of neutrophilic leukocyte percentage and HMGB1 than those of mild cases （P 〈 0. 01 ）. But the level of RAGE showed no statistical significance among mild, moderate or severe asthma cases （ P 〉 O. 05 ）. The post-treatment levels of neutrophilic leukocyte percentage, HMGB1 and RAGE were lower as compared with the pre-treatment ones （ P 〈 0. 01 ） . These three parameters in uncontrolled cases were higher than those in completely controlled cases （P 〈 0. 05 ） ; in asthma group, both HMGB1 and RAGE had a negative correlation with FEV1% （ r = - 0. 830, r = - 0. 632, P 〈 0.01 ） ; in induced sputum, both HMGB1 and RAGE had a positive correlation with FEV1% （r = 0. 820, r = 0. 623, P 〈 0. 01 ）. The levels of HMGB1 and RAGE were positively correlated （ r = 0. 929, P 〈 O. 01 ）. Conclusion Both HMGB1 and RAGE participate in the inflammatory process of asthmatic airway. HMGB1 is correlated with the severity of asthma. And the levels of HMGB1 and RAGE in induced sputum may be employed as reference indices for the observation of therapeutic effects.