基于“痹-虚”病机中药对肺纤维化大鼠TGF-β/Smads信号通路的影响

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目的:研究通痹补肺方对肺纤维化大鼠的保护作用及可能的作用机制。方法:60只大鼠随机分为3组,空白组、模型组和中药组(通痹补肺方组),每组20只。除空白组外,其余各组用博来霉素气管内注射造成肺纤维化模型,造模28天后给药,中药组给予通痹补肺方12.4g/kg/d灌胃,空白组及模型组给予等体积生理盐水灌胃,连续给药28天。首先测定大鼠肺功能(FVC、FEV0.3/FVC、PEF、MVV、Cdyn),继之处死大鼠行肺组织病理学观察,同时应用免疫组化及免疫印迹法测定大鼠肺组织中TGF-β、Smad3、Smad7及Ⅰ、Ⅲ型胶原的含量。结果:光镜下显示,模型组大鼠正常肺泡结构破坏,多数肺泡壁增厚,可见纤维组织增生,伴有少许炎性细胞浸润,呈中重度纤维化样改变,中药组大鼠肺纤维化及肺泡炎性程度均较模型组明显减轻。各组大鼠肺功能比较,FVC、FEV0.3/FVC、PEF、MVV值各组之间比较均无差异(P>0.05);与模型组比较,中药组及空白组Cdyn值明显升高(P<0.05),中药组及空白组肺组织中Ⅰ、Ⅲ型胶原含量明显降低(P<0.05),TGF-β、Smad3含量明显下降(P<0.05),Smad7含量明显上升(P<0.05);与空白组比较,中药组及模型组Cdyn值明显降低(P<0.05),中药组及模型组肺组织中Ⅰ、Ⅲ型胶原含量明显降低(P<0.05),TGF-β、Smad3含量明显下降(P<0.05),Smad7含量明显上升(P<0.05)。结论 :通痹补肺方能够通过抑制肺纤维化大鼠TGF-β及Smad3的异常增高,同时提高肺纤维化大鼠Smad7水平,达到抑制肺纤维化大鼠胶原异常增殖的作用。 Objective: To study the protective effect of Tongbi Bufei Recipe on pulmonary fibrosis in rats and its possible mechanism. Methods: Sixty rats were randomly divided into three groups: blank group, model group and TCM group (Tongbubuxuetang group), 20 rats in each group. In addition to the blank group, the other groups with bleomycin intratracheal injection caused by pulmonary fibrosis model, the model 28 days after administration, the Chinese medicine group Tongbi Bu Bufei Fang given 12.4g / kg / d gavage, the blank group and model Group given equal volume of saline irrigation, continuous administration of 28 days. First, the pulmonary function (FVC, FEV0.3 / FVC, PEF, MVV, Cdyn) in rats was measured, followed by the pathological observation of lungs in rats. Immunohistochemistry and Western blotting were used to detect the expression of TGF -β, Smad3, Smad7 and type Ⅰ, Ⅲ collagen content. Results: Under the light microscope, the normal alveolar structure was destroyed and most of the alveolar wall was thickened in the model group. The fibrous tissue hyperplasia was observed with a little infiltration of inflammatory cells, with moderate and severe fibrosis changes. The pulmonary fibrosis And alveolar inflammation than the model group were significantly reduced. Compared with the model group, the Cdyn values ​​in the TCM group and the blank group were significantly higher than those in the model group (P <0.05), while there was no significant difference in the FVC, FEV0.3 / FVC, PEF and MVV between the groups (P <0.05). The contents of type Ⅰ and type Ⅲ collagen in the lung tissue of the Chinese medicine group and the blank group were significantly decreased (P <0.05), while the contents of TGF-β and Smad3 were significantly decreased (P <0.05) (P <0.05). Compared with the blank group, the Cdyn values ​​of the Chinese medicine group and the model group were significantly decreased (P <0.05), and the contents of type Ⅰ and type Ⅲ collagen in the Chinese herbs group and the model group were significantly decreased (P <0.05), while the content of Smad7 increased significantly (P <0.05). CONCLUSION: Tongbi Bu Bu Fang can inhibit the abnormal increase of TGF-β and Smad3 in rats with pulmonary fibrosis and increase the level of Smad7 in pulmonary fibrosis in rats, which can inhibit the abnormal proliferation of collagen in pulmonary fibrosis rats.
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