Abstract: Objective　To investigate the influence of maimendong decoction（MD） on the expression levels of TGF-β1，MMP-9 and TIMP-1 and pathological changes in lung tissue of a rat model of bleomycin-induced pulmonary fibrosis．Methods　This study was implemented from November 2016 to October 2017.80 male SD rats were equally randomized into the control group，model group，MD group，and prednisone group by random number table，with 20 in each.The control group received intragastric administration of distilled water 1.1 ml/100 g，and the latter three groups received intragastric administration of distilled water（1.1 ml/100 g），MD（1.1 g?ml-1?100 g-1），prednisone（5 mg/kg），once daily，respectively at 24 h after modeling pulmonary fibrosis with bleomycin.On the 7th and 14th days of intervention，half rats of each group were sacrificed for collecting lung tissue for detecting the severity of pulmonary alveolitis and the degree of pulmonary fibrosis using HE and Masson staining，and for determining the expression levels of TGF-β1，MMP-9 and TIMP-1 with immunohistochemical staining．Results　The MD group showed swelled epithelial cells in bronchioles and degenerative vacuoles in lung parenchyma and mild to moderate alveolitis on the 7th day of intervention，and presented aggravated alveolitis and pulmonary fibrosis on the 14th day of intervention.The model group demonstrated disorganized lung tissue，with massive deposition of deep blue mature collagen fibers around the small vessels，thickened alveolar septum and wall，and thickened collagen fibers in lung interstitium，which were more notable on the 14th day of intervention.Between the 7th and 14th days of intervention，the collagen fibers accumulated faster in the model group than in the MD group and prednisone group.On the 7th and 14th days of intervention，the pulmonary inflammation integral and degree of fibrosis in the MD group were milder than those of the model group（P<0.05）．The expression levels of TGF-β1，MMP-9 and TIMP-1 in the MD group were lower than those of the model group（P<0.05），but did not differ greatly from those of the prednisone group（P>0.05）．Conclusion　MD showed significant effects on alleviating the degree of bleomycin-induced pulmonary alveolitis and fibrosis，which may be related to the improvement of abnormal metabolism of extracellular matrix by inhibiting the expression levels of TGF-β1，MMP-9 and TIMP-1 in lung parenchyma.

Key words: Pulmonary fibrosis；Maimendong decoction；Alveolitis, fibrosing；Transforming growth factor beta 1；Matrix metalloproteinase 9

摘要： 目的　探讨麦门冬汤对肺纤维化模型大鼠转化生长因子β1（TGF-β1）、基质金属蛋白酶9（MMP-9）和基质金属蛋白酶组织抑制剂1（TIMP-1）表达和肺组织病理变化的影响。方法　2016年11月—2017年10月，选取80只雄性SD大鼠，采用随机数字表法分为4组，每组各20只。空白组予蒸馏水1.1 ml/100 g灌胃；模型组造模24 h后予蒸馏水1.1 ml/100 g灌胃；麦门冬汤组造模24 h后予麦门冬汤（1.1 g?ml-1?100 g-1），1次/d灌胃治疗；泼尼松组造模24 h后予泼尼松（5 mg/kg），1次/d灌胃治疗。每组分别于造模后第7、14天处死10只大鼠取肺组织，HE和Masson染色法评估肺组织肺泡炎症和纤维化程度，免疫组化法检测TGF-β1、MMP-9、TIMP-1表达水平。结果　麦门冬汤组第7天肺实质内表现为细支气管上皮细胞肿胀，出现空泡变化，呈轻、中度肺泡炎改变；第14天可见炎症、纤维化程度增加。模型组肺组织结构紊乱，小血管周围见深蓝色成熟胶原纤维的显著沉积，在第14天尤为明显，其中肺泡间隔和肺泡壁明显增厚，肺间质中胶原纤维增厚。但麦门冬汤组及泼尼松组第7、14天胶原纤维沉积较为缓慢。第7、14天，麦门冬汤组肺泡炎症积分及纤维化程度均低于模型组，TGF-β1、MMP-9和TIMP-1表达水平均低于模型组（P<0.05），而与泼尼松组无差异（P>0.05）。结论　麦门冬汤在肺纤维化模型大鼠中显示出缓解肺泡炎症和抗纤维化特性，其机制可能是抑制肺组织中TGF-β1、MMP-9与TIMP-1表达水平，从而调整细胞外基质的异常代谢。

关键词: 肺纤维化, 麦门冬汤, 肺泡炎, 纤维化, 转化生长因子&beta, 1, 基质金属蛋白酶9