银杏叶提取物通过miR-133a调节TGFβ1诱导的乳鼠心肌成纤维细胞增殖的作用及机制  

Ginkgo biloba extract regulates TGFβ1-induced myocardial fibroblast proliferation of neonatal rats through miR-133a

作　　者：姚雨彤 钱宇 游赣花 何尤夫 YAO Yutong;QIAN Yu;YOU Ganhua;HE Youfu(Department of Cardiovascular Medicine,Guizhou Provincial People's Hospital,Guiyang 550000,Guizhou,China;Guizhou Clinical Medical Research Centre for Cardiovascular Diseases,Guizhou Provincial Clinical Medical Research Centre for Cardiovascular Diseases,Guiyang 550000,Guizhou,China;Department of Cardiovascular Medicine,the Second Affiliated Hospital of Zunyi Medical University,Zunyi 563100,Guizhou,China;Department of Research,The Second People's Hospital of Guizhou Province,Guiyang 550000,Guizhou,China)

机构地区：[1]贵州省人民医院心血管内科,贵州贵阳550000 [2]贵州省人民医院贵州省心血管疾病临床医学研究中心科研处,贵州贵阳550000 [3]遵义医科大学第二附属医院心血管内科,贵州遵义563100 [4]贵州省第二人民医院科研处,贵州贵阳550000

出　　处：《贵州医科大学学报》2024年第7期975-981,共7页Journal of Guizhou Medical University

基　　金：国家自然科学基金地区项目(82260061);贵州省科技厅科学技术基金(黔科合基础-ZK〔2023〕一般217,黔科合基础-ZK〔2021〕一般358);贵州省卫生健康委科学技术基金(gzwkj2021-102)。

摘　　要：目的研究银杏叶提取物(GBE)对转化生长因子β1(TGFβ1)诱导的乳鼠心肌成纤维细胞增殖的作用及机制,探索miR-133a在心肌成纤维细胞增殖中的作用。方法使用TGFβ1诱导乳鼠心肌成纤维细胞增殖,并加入GBE与细胞模型共培养;使用CCK8、流式细胞术分别检测细胞增殖活性和细胞周期;Mimic和siRNA构建miR-133a过表达及抑制表达的模型,并使用RT-PCR检测各组细胞中miR-133a、TGFβ1及TGFβ受体表达。结果TGFβ1可促进心肌成纤维细胞活性、提高心肌成纤维细胞由G0/G1期进入S期的比例,而GBE则可明显改善TGFβ1造成的相关影响;TGFβ1诱导的心肌成纤维细胞模型中,GBE处理或过表达miR-133a均可明显改善TGFβ1诱导的心肌成纤维细胞增殖及TGFβ受体的mRNA水平表达,而在细胞模型中抑制miR-133a表达,则会部分抵消GBE对于细胞增殖的调节作用。结论GBE可明显改善TGFβ1诱导的心肌成纤维细胞增殖,这或与其上调miR-133a并抑制TGFβ受体表达有关。Objective To investigate the role of ginkgo biloba extract(GBE)in TGFβ1-induced myocardial fibroblast proliferation of neonatal rats and its mechanism,and explore the role of miR-133a in myocardial fibroblast proliferation.Methods TGFβ1 was used to induce myocardial fibroblast proliferation of neonatal rats to establish cell proliferation model.GBE was added to the above cell proliferation model.CCK8 assay and flow cytometry were applied to detect cell proliferation and cell cycle,respectively.Mimic and siRNA were used to construct a model for overexpression and inhibition of miR-133a,respectively.RT-PCR was used to detect the expressions of miR-133a,TGFβ1,and TGFβreceptor.Results TGFβ1 promoted the viability of myocardial fibroblasts and increased the proportion of myocardial fibroblasts entering S phase from G0/G1 phase,while GBE significantly antagonized the TGFβ1-induced effects.In TGFβ1-induced myocardial fibroblast model,GBE treatment or overexpression of miR-133a significantly inhibited TGFβ1-induced myocardial fibroblast proliferation and mRNA expression of TGFβreceptor,while inhibiting miR-133a expression in the cell model partially counteracted the regulatory effect of GBE on cell proliferation.Conclusion GBE may remarkably improve myocardial fibroblast proliferation induced by TGFβ1.It may be attributed to the upregulation of miR-133a and inhibition of TGFβreceptor expression by GBE.

关 键 词：银杏叶提取物 心肌成纤维细胞 心肌纤维化 转化生长因子Β1 细胞增殖 miR-133a 

分 类 号：R541.4[医药卫生—心血管疾病]