HMGB1表达水平与慢性阻塞性肺病大鼠模型气道、肺血管重构的关系及其临床意义

The correlation between the expression of HMGB1 and the airway remodeling,pulmonary vascular reconstruction in rats with chronic obstructive pulmonary disease and clinical significance

目的:探讨慢性阻塞性疾病(Chronic obstructive pulmonary disease,COPD)大鼠模型气道、肺血管重构与高迁移率族蛋白B1(High mobility group protein B1,HMGB1)表达水平的相关性。方法:健康无特定病原体(Specific pathogen free,SPF)级SD雄性大鼠24只,分为3组,每组8只。正常对照组(A):正常饲养6周;COPD组(B):第1、14天经气道内注入脂多糖(Lipopolysac-charide,LPS)溶液,200μg/次,烟熏1 h/d,共6周;COPD并低氧组(C):第1、14天经气道内注入LPS,200μg/次,熏香烟1 h/d,共6周,实验最后2周在烟熏的同时,给予18%低氧8 h/d。造模结束后观测各组大鼠气道炎症、重构以及肺小动脉的病理改变,用Western blot检测各组肺组织中HMGB1蛋白的表达。结果:①B、C组气道重构指标细支气管管壁厚度与气管外径比值(MT%)、管壁面积和气管总面积比值(MA%)与A组比较均明显增高(P<0.05)。②B、C组肌化型动脉百分比与A组相比增多(P<0.05);C组肺小动脉管壁厚度与血管外径比值(WT%)以及管壁面积与血管总面积比值(WA%)与A组相比较均增大(P<0.05)。③Western blot电泳结果显示:B、C组HMGB1蛋白表达水平与A组相比明显增强(P<0.05),C组较B组HMGB1蛋白表达增强(P<0.05)。结论:随着COPD疾病进展出现进行性加重的气道、肺血管重构,同时HMGB1的表达逐渐增强,说明HMGB1的表达与COPD的气道、肺血管重构有关。

Objective：To investigate the correlation between the expression of HMGB1 and the airway remodeling,pulmonary vascular reconstruction in COPD.Methods：24 SD rats were divided into 3 groups randomly.Healthy control group（Group A）：rats were bred for 6 weeks in normal circumstance before controlling a test later.COPD group（Group B）：200 μg LPS was instilled intratracheally once on d1 and d14 in all rats.These rats were exposed to cigarette smoke 1 h/d for 6 weeks.COPD and chronic hypoxia group（Group C）：200 μg LPS was instilled intratracheally once on d1 and d14 and the rats were exposed to cigarette smoke 1 h/d for 6 weeks.In the last 2 weeks chronic hypoxia（FiO2=0.18） 8 h/d were performed simultaneously.We studied airway wall remodeling and morphologic changes of small pulmonary arteries.The positive expression of HMGB1 in lung tissue was examined by Western blot.Results：①Compared with group A,the ratio of bronchial wall thickness over bronchial external diameter（MT%）and the ratio of bronchial wall area over total area（MA%）were significantly higher in group BC（P0.05）.②The muscularization of intra-aveolar arteries in group BC was more severe than that in group A（P0.05）.The cross-sectional medial vascular wall area of pulmonary arteries was increased significantly in group C（P0.05）.③Western blot showed that compared with group A,the expression of HMGB1 protein in group BC was significantly increased（P0.05）.The expression of HMGB1 protein in group C was higher than that of group B（P0.05）.Conclusion：With the progression of COPD,the airway remodeling and pulmonary vascular reconstruction aggravates progressively,while the expression of HMGB1 is increased in lung tissue.There may be some relevance between the expression of HMGB1 and the airway remodeling,and pulmonary vascular reconstruction.