血府逐瘀汤对肺纤维化大鼠肺组织上皮间质转化的影响及其机制研究

Effects of Xuefu Zhuyu Tang on Epithelial-mesenchymal Transition of Lung Tissue in Pulmonary Fibrosis Model Rats and Mechanism Study

目的:研究血府逐瘀汤对肺纤维化(PF)大鼠肺组织上皮间质转化(EMT)的影响,并探讨其可能机制。方法:将48只雄性SD大鼠随机分为正常组、模型组、地塞米松组(0.000405 g·kg^-1·d^-1)和血府逐瘀汤高、中、低剂量组(14.04、7.02、3.51 g·kg^-1·d^-1),每组8只。除正常组外,其余各组大鼠均于气管内滴注博来霉素溶液建立PF模型。造模后第2天开始灌胃给药,正常组和模型组予蒸馏水溶液(10 mL·kg^-1·d^-1);各给药组灌胃相应药物,每日1次,连续28 d。末次给药24 h后,采用免疫组化法检测大鼠肺组织中E-钙黏蛋白(E-cadherin)和α-平滑肌肌动蛋白(α-SMA)的表达情况,采用Western blot法检测大鼠肺组织中TGF-β1、Smad3的表达情况。结果:模型组大鼠肺组织E-cadherin表达显著低于正常组(P<0.01),而α-SMA、TGF-β1、Smad3表达均显著高于正常组(P<0.01);与模型组比较,血府逐瘀汤高、中、低剂量组肺组织E-cadherin表达显著升高(P<0.05或P<0.01),而α-SMA、TGF-β1、Smad3表达均显著降低(P<0.05或P<0.01);与地塞米松组比较,血府逐瘀汤低剂量组的E-cadherin表达显著降低(P<0.05),而α-SMA、TGF-β1、Smad3表达均显著升高(P<0.05或P<0.01)。结论:血府逐瘀汤可通过干预上皮间质转化来减轻肺纤维化,其机制可能与抑制TGF-β1/Smad3信号通路有关。

Objective To investigate the effects of Xuefu Zhuyu Tang on epithelial-mesenchymal transition(EMT)of lung tissue in pulmonary fibrosis(PF)model rats,and to explore its potential mechanism.Methods 48 Male SD rats were randomly divided into normal group,model group,dexamethasone group(0.000405 g·kg^-1·d^-1),Xuefu Zhuyu Tang high-dose,medium-dose and low-dose groups(14.04、7.02、3.51 g·kg^-1·d^-1),with 8 rats in each group.Except for normal group,other groups were given endotracheal injection of bleomycin to induce PF model.On the second day after modeling,normal group and modelgroup were given water intragastrically(10 mL·kg^-1·d^-1),administration groups were given relevant medicine intragastrically,once a day,for consecutive 28 days.24hs after last medication,the expression of E-cadherin andα-SMA in lung tissue of rats were detected by immunohistochemistry method.The expression of TGF-β1 and Smad3 were detected by Western blotting assay.Results Compared with normal group,the expression of E-cadherin were decreased significantly in lung tissue of model group(P<0.01),while the expression ofα-SMA,TGF-β1 and Smad3 were increased significantly(P<0.01).Compared with model group,the expression of E-cadherin in lung tissue of rats were increased significantly in Xuefu Zhuyu Tang high-dose,medium-dose and low-dose groups(P<0.05 or P<0.01),while the expression ofα-SMA,TGF-β1 and Smad3 were decreased significantly(P<0.05 or P<0.01).Compared with dexamethasone group,the expression of E-cadherin were decreased significantly,the expressipon ofα-SMA,TGF-β1 and Smad3 were increased significantly(P<0.01).Conclusion Xuefu Zhuyu Tang can relieve PF of model rats by intervening in EMT,the mechanism of which may be associated with inhibiting TGF-β1/Smad3 signaling pathway.