基于miRNA测序探究瓜蒌薤白半夏汤对动脉粥样硬化小鼠Epsin1-FGFR1通路调节机制研究  

MicroRNA analysis of the regulatory effects of Gualou Xiebai Banxia Decoction on the Epsin1-fibroblast growth factor receptor 1 pathway in atherosclerotic mouse

作　　者：王兆博 潘熠 林谦[1] WANG Zhaobo;PAN Yi;LIN Qian(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700

出　　处：《中国比较医学杂志》2024年第11期26-33,共8页Chinese Journal of Comparative Medicine

基　　金：国家中医药管理局高水平中医药重点学科建设项目(zyy201xk-2023253)。

摘　　要：目的本研究旨在评估瓜蒌薤白半夏汤(Gualou Xiebai Banxia Decoction,GXBD)对动脉粥样硬化(atherosclerosis,AS)模型小鼠的治疗效果,并探讨其作用机制。方法实验采用ApoE^(-/-)雄性小鼠,通过16周高脂饮食诱导AS模型。小鼠随机分为模型组、对照组、不同剂量的GXBD治疗组及降脂药组。通过HE染色和油红染色观察动脉壁和斑块的变化,并通过短链RNA(microRNA,miRNA)测序分析GXBD的调控作用。应用蛋白免疫印迹实验(Western blot)和免疫荧光实验验证关键蛋白的表达变化。结果结果显示,GXBD能够显著减少动脉斑块的形成。miRNA测序分析发现,GXBD对多个与AS相关的miRNA基因具有调控作用,尤其是通过调节表皮生长因子底物蛋白1(epidermal growth factor receptor pathway substrate 15(EPS15)interacting protein 1,Epsin1)和成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)等关键蛋白的表达,对AS产生潜在治疗效果。进一步的Western blot和免疫荧光实验验证了这些调控作用。结论研究结果表明,GXBD可通过调控miR-3102-5p、miR-3547-5p、miR-7080-5p下调AS小鼠主动脉内皮Epsin1表达,同时上调FGFR1蛋白表达,抑制内皮细胞的间充质转化,在AS的治疗中具有显著疗效。Objective This study aims to evaluate the therapeutic effect of Gualou Xiebai Banxia Decoction(GXBD)on an atherosclerosis(AS)mouse model and explore its underlying mechanism.Methods Male ApoE^(-/-)mice were fed a high-fat diet for 16 weeks to induce the AS model.Mice were divided into a model group,control group,GXBD treatment groups(at different doses),and a lipid-lowering drug group.Histological assessments(HE and Oil Red staining)were performed to observe arterial changes.MicroRNA(miRNA)sequencing was used to analyze the regulatory effect of GXBD.Western blot and immunofluorescence were applied to confirm key protein expression.Results GXBD significantly reduced plaque formation and regulated several AS-related miRNAs,notably impacting Epsin1 and FGFR1 protein expression.Western blot and immunofluorescence further validated these effects.Conclusions GXBD demonstrated a therapeutic effect on AS by regulating miR-3102-5p,miR-3547-5p,and miR-7080-5p,downregulating Epsin1,and upregulating FGFR1,thereby inhibiting endothelial-to-mesenchymal transition.

关 键 词：冠心病 动脉粥样硬化 MIRNA 瓜蒌薤白半夏汤 

分 类 号：R-33[医药卫生]