瓜蒌薤白汤对肺纤维化早期阶段肺组织中TGF-β、Smad3、Smad7表达的影响

目的:探讨瓜蒌薤白汤防治肺纤维化的作用机理。方法:72只SD大鼠随机分为4组,即博莱霉素组、瓜蒌薤白汤组、泼尼松组、正常组,每组18只。用博莱霉素诱导大鼠肺纤维化模型后,用药组每天灌胃瓜蒌薤白汤,分别于第7天、第14天后处死各组大鼠,观察、比较各组大鼠肺泡炎、肺纤维化程度和肺组织中转化生长因子-β(transforming growth factor,TGF-β)、Smad3、Smad7的表达。结果:光学显微镜下,正常组大鼠肺组织正常;博莱霉素组大鼠第7天肺泡间隔增厚,肺泡腔内有炎性细胞浸润,第14天呈1级肺泡炎改变和2级、3级肺组织纤维化;瓜蒌薤白汤组大鼠肺组织炎性改变和纤维化程度较博莱霉素组减轻,炎性细胞浸润减少,部分呈1级纤维化改变。免疫组织化学结果显示:与正常组比较,第7天和第14天博莱霉素组TGF-β、Smad3表达水平升高,Smad7表达下降(P0.05);与博莱霉素组比较,4 g·kg~(-1)瓜蒌薤白汤可使TGF-β、Smad3表达下降(P0.05),而Smad7表达增高(P0.05)。Real time-PCR结果显示:与正常组比较,第7天和第14天博莱霉素组TGF-β、Smad3表达水平明显升高(P0.05),Smad7表达下降(P0.05);与博莱霉素组比较,4 g·kg~(-1)瓜蒌薤白汤可使TGF-β和Smad3表达下降(P0.05),Smad7表达增高(P0.05)。结论:瓜蒌薤白汤能明显减轻博莱霉素所致的大鼠肺泡炎,有效调控TGFβ-Smad信号通路介导的致纤维化作用,进而起到抗纤维化的作用。

Effects of Gualouxiebai Decoction on Expression of TGF-beta,Smad3 and Smad7 in Lung Tissue of Early Pulmonary Fibrosis

Objective:To explore the mechanism of Gualouxiebai Decoction (GLXBD) in prevention and treatment of pulmonary fibrosis.Methods:Seven-two SD rats were randomly divided into four groups:Bleomycin model group,Gualouxiebai Decoction group,Prednisone group and blank group,with 18 rats in each group.After the establishment of bleomycin-induced rat pulmonary fibrosis model,the rats in each group were sacrificed on the 7th day and the 14th day.Each group of rats in degree of alveolitis and pulmonary fibrosis and the levels of transforming growth factor-β1 (TGF-β),Smad3 and Smad7 in lung tissue were observed and compared.Results:Under the optical microscope,the lung tissue of the control group was normal.In the bleomycin model group,the alveolar septum was thickened at the 7th day,the inflammatory cells were infiltrated in the alveolar cavity,the alveolar inflammation was changed on the 14th day,and the level of lung fibrosis were grade 2 or 3.The inflammatory changes and fibrosis of the lung tissue of Gualouxiebai Decoction group were less than that of the model group,and the infiltration of inflammatory cells decreased and the fibrosis changed to grade 1.Immuno-histochemical results suggested that the expression of TGF-β and Smad3 significantly increased and the expression of Smad7 significantly decreased in the bleomycin model group(P ＜ 0.05).Compared with that of the normal control group,the expression of Smad7 significantly increased (P ＜ 0.05).The expression of TGF-β significantly decreased while that of Smad3 and the Smad7 expression significantly increased (P ＜ 0.05).The expression of TGF-β and Smad3 in the model group was significantly higher than that in the normal group (P ＜ 0.05),and the expression of Smad7 decreased compared with that the normal group (P ＜ 0.05).Compared with that of the model group,the expression of TGF-β and Smad3 significantly decreased (P ＜ 0.05) and the expression of Smad7 significantly increased (P ＜ 0.05).Conclusion:Gualouxiebai decoction can significantly reduce the alveolitis caused by bleomycin,effectively regulate the TGFβ-Smad signaling pathway mediated fibrosis,and thus play the role of anti-fibrosis.