温阳化浊通络方抑制系统性硬化病EndoMT的机制研究

THE MECHANISM OF WENYANG HUAZHUO TONGLUO FORMULA SUPPRESSING ENDOMT IN SYSTEMIC SCLEROSIS

目的:研究温阳化浊通络方抑制系统性硬化病(Systemic sclerosis,SSc)肺血管内皮细胞内皮-间充质转化(Endothelium-mesenchymal transformation,EndoMT)的效应和潜在分子机制。方法:利用博来霉素构建SSc小鼠模型,然后分别利用温阳化浊通络方或HIF-1α抑制剂KC7F2处理。采用masson染色观察小鼠肺组织纤维化程度。采用免疫组化检测小鼠肺组织和细胞中HIF-1α、Foxm1、smad3、VE-Cadherin、vimentin的蛋白表达水平。结果:在SSc小鼠模型中,温阳化浊通络方和KC7F2能够显著抑制小鼠肺组织的纤维化,并且下调肺组织中HIF-1α、Foxm1、smad3、vimentin的蛋白表达水平(P<0.05),同时上调VE-cadherin的蛋白表达水平(P<0.05)。结论:温阳化浊通络方能够抑制SSc肺血管内皮细胞EndoMT,其分子机制与其抑制HIF-1α/Foxm1/Smad3信号通路有关。

Objective:To investigate the effect and potential molecular mechanism of Wenyang Huazhuo Tongluo formula to inhibit the endothelium-mesenchymal transformation(EndoMT)of pulmonary vascular endothelial cells in Systemic sclerosis(SSc).Methods:The SSc mouse model was constructed using bleomycin and then treated with Wenyang Huazhuo Tongluo formula or HIF-1αinhibitor KC7F2,respectively.Masson staining was used to observe the fibrosis of mouse lung tissues.Immunohistochemistry was used to detect the protein expression levels of HIF-1α,Foxm1,smad3,VE-Cadherin and vimentin in lung tissues.Results:In the SSc mouse model,Wenyang Huazhuo Tongluo formula and KC7F2 significantly inhibited fibrosis of lung tissues and down-regulated the protein expression levels of HIF-1α,Foxm1,smad3,and vimentin in lung tissues(P<0.05),while up-regulating VE-cadherin(P<0.05).Conclusion:Wenyang Huazhuo Tongluo formula can inhibit EndoMT of pulmonary vascular endothelial cells in SSc,and the molecular mechanism is related to its inhibition of HIF-1α/Foxm1/Smad signaling pathway.