二氧化硫对慢性变应性气道炎症、气道上皮下纤维化的促进作用

Promotion of chronic allergic airway inflammation and subepithelial fibrosis by prior sulfur dioxide inhalation

目的研究SO2所造成的急性气道炎症、上皮损伤对卵白蛋白反复激发致敏小鼠慢性变应性气道炎症、气道上皮下纤维化（subepithelial fibrosis，SEF）的影响。方法吸入50ppm SO2诱发急性气道炎症；卵白蛋白反复激发4、8周，观察首次激发前吸入、未吸入SO2的小鼠支气管肺泡灌洗液（bronehoalveolar lavage fluid，BALF）细胞学、内皮素1（endothelin-1，ET-1）和转化生长因子β1（transforming growth factor-β1，TGF-β1）水平、肺组织羟脯氨酸（Hyp）含量、气道上皮基底膜下纤维面积及气道组织学改变。结果吸入SO2导致急性中性粒细胞性气道炎症、上皮损伤，卵白蛋白反复激发诱发慢性变应性气道炎症、SEF，二者均导致BALF中ET-1、TGF-β1水平增高。与同期单纯激发组相比，损伤激发组SEF出现更早，气道炎症、SEF更显著，肺组织Hyp与BALF中TGF-β1呈正相关。结论预先吸入SO2导致的急性气道炎症、上皮损伤能加剧慢性变应性气道炎症，促进并加重SEF，可能与气道炎症、上皮损伤过程中气道微环境ET-1、TGF-β1表达上调有关。

Objective To investigate the effects of acute airway inflammation and epithelial injury caused by prior exposure to SOz on development of chronic allergie airway inflammation and subepithelial fibrosis（SEF） in ovalbumin（Ova）-sensitized and challenged mice. Methods Mice were subjected to exposure to 50 ppm SO2, or prolonged Ova-challenge for 4 or 8 weeks with or without prior exposure to SO2. Bronehoalveolar lavage fluid （BALF） cytology, endothelin-1 （ ET- 1 ） and transforming growth factor-β1 （TGF-β1） levels,lung hydroxyproline（Hyp） content, morphometrie study of fibrotie area beneath basement membrane and lung histology were studied. Results Brief exposure to SO2 elicited acute neutrophilic airway inflammation and epithelial sloughing. Prolonged Ova-challenge caused chronic allergic airway inflammation and SEF. ET-1 and TGF-β1 levels in BALF increased during acute and chronic airway inflammations. Prior exposure to SO2 aggravated chronic allergic inflammation, facilitated and exaggerated SEF. There was a positive correlation between lung Hyp and BALF TGF-β1. Conclusions SO2-elicited acute airway inflammation and epithelial damage could promote chronic allergic inflammation, facilitate and exaggerate SEF,which is possibly associated with the upregulation of ET-1 and TGF-β1 in airway microenvironment during airway inflammation and epithelial injury.