高迁移率族蛋白B1和Toll样受体4与哮喘气道炎症的关系及维生素D的作用

摘要

Objective To evaluate the relationship of high mobility group box 1 (HMGB1) and TLR4 with airway inflammation and the role of vitamin D.Methods Totally 24 BALB/c mice were randomly divided into control group,asthma group,and 1,25-(OH)2D3 group,each having 8 mice.The pathological changes in lung tissue of the mice were observed by hematoxylin-eosin (HE) staining,bronchial wall thickness was measured with computer pathological image analysis system software.The expressions of HMGB1 and TLR4 in lung tissue were detected by immunohistochemical method.Bronchoalveolar lavage fluid (BALF) was collected for cytological examination;the contents of HMGB1,TLR4,IL-4 and IFN-γ in BALF and the peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA).Results The expressions of HMGB1 and TLR4 in lung tissue were stronger in asthma group,but weaker in intervention group.The total number of leukocytes as well as the percentages of eosinophils,neutrophils and lymphocytes increased significantly in BALF in asthma group,but significantly decreased in intervention group (all P ＜ 0.05).The ratio of monocyte/macrophage significantly decreased in asthma group,but increased significantly in intervention group (P＜0.05).The contents of HMGB1,TLR4 and IL-4 in BALF and the peripheral blood were significantly higher in asthma group than in control and intervention groups,whereas IFN-γ level was significantly lower than that in control and intervention groups (all P＜0.05).HMGB1 and TLR4 contents had a positive correlation with the total number of cells and IL-4 concentration in BALF,respectively (r1=0.796,0.730;r2=0.695,0.648;all P＜0.05).Conclusion HMGB1 and TLR4 were associated with airway inflammation and immune disorders.An appropriate amount of 1,25-(OH)2D3 can relieve airway inflammation,which may be associated with regulating Th1/Th2 cells balance.%目的 探讨高迁移率族蛋白B1(HMGB1)和Toll样受体4(TLR4)与气道炎症的关系及维生素D的作用.方法 BALB/c小鼠随机分为对照组、哮喘组和1,25-(OH)2D3干预组(每组8只).采用HE染色观察小鼠肺组织病理学变化并应用计算机图像系统测定支气管壁厚度,采用免疫组化法观察肺组织HMGB1和TLR4表达,同时收集支气管肺泡灌洗液(BALF)和外周血,将BALF进行细胞学检测,用酶联免疫吸附法(ELISA)测定BALF和外周血中HMGB1、TLR-4、白介素-4(IL-4)和干扰素-γ(IFN-γ)含量.结果 哮喘组小鼠肺组织HMGB1和TLR4表达较强,干预组表达较弱.哮喘组BALF中白细胞总数及嗜酸性粒细胞、中性粒细胞和淋巴细胞比例明显升高,单核/巨噬细胞比例明显下降(均为P＜0.05);干预组BALF中白细胞总数及嗜酸性粒细胞、中性粒细胞和淋巴细胞比例明显下降,单核/巨噬细胞比例明显上升(均为P＜0.05).哮喘组BALF和外周血中HMGB1、TLR4和IL-4含量均明显高于对照组,IFN-γ含量均明显低于对照组(均为P＜0.05);干预组BALF和外周血中HMGB1、TLR4和IL-4含量均明显低于哮喘组,IFN-γ含量明显高于哮喘组(均为P＜0.05).BALF中HMGB1和TLR4含量分别与细胞总数和IL-4浓度均呈正相关(r1为0.796、0.730;r2为0.695、0.648;均为P＜0.05).结论 HMGB1和TLR4与气道炎症和免疫紊乱有关;适量1,25-(OH)2D3可减轻气道炎症,可能与调节Th1/Th2细胞平衡有关.