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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
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摘要 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.
作者 李凯 王倩 段培培 卞华 Kai;WANG Qian;DUAN Pei-pei;BIAN Hua(Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation,Nanyang Institute of Technology,Nanyang 473004,China;Zhang Zhongjing College of Chinese Medicine,Nanyang Institute of Technology,Nanyang 473004,China;College of Orthopaedics and Traumatology,Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处 《南阳理工学院学报》 2023年第6期118-122,128,共6页 Journal of Nanyang Institute of Technology
基金 国家自然科学基金面上项目(82074415) 河南省科技攻关计划项目(222102310258) 中原科技创新领军人才项目(234200510006)。
关键词 温阳化浊通络方 系统性硬化病 HIF-1α/Foxm1/Smad信号通路 内皮-间充质转化 Wenyang Huazhuo Tongluo formula systemic sclerosis HIF-1α/Foxm1/Smad signaling pathway endothelial-mesenchymal transition
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