基于心脏成纤维细胞microRNA-22/TGFβ-1信号通路研究红花-葶苈子对心肌纤维化的抑制作用  

Research on Mechanism of Drug Pair of Honghua(Carthamus tinctorius L) and Tinglizi(Lepidium apetalum Willd) Inhibiting Myocardial Fibrosis Based on MicroRNA-22/TGFβ-1 Pathway in Cardiac Fibroblasts

作　　者：王咏 马度芳 王成[2] 李晓[1] 王震[1] WANG Yong;MA Dufang;WANG Cheng;LI Xiao;WANG Zhen(Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong,China;Zaozhuang Municipal Hospital,Zaozhuang 277100,Shandong,China)

机构地区：[1]山东中医药大学附属医院,山东济南250014 [2]枣庄市立医院,山东枣庄277100

出　　处：《辽宁中医杂志》2020年第12期171-175,I0020,共6页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81673970)。

摘　　要：目的观察红花-葶苈子药对对心肌梗死后心衰小鼠心肌纤维化的抑制作用,并探寻其治疗作用的可能机制。方法取40只C57BL/6雄性小鼠,其中20只结扎左前降支制备心肌梗死后心衰小鼠模型。分别从C57BL/6雄性小鼠分离心脏成纤维细胞和心脏微血管内皮细胞,并使用Ang II刺激其过度增殖。利用Masson染色评价心衰小鼠心肌纤维化程度。Real time-PCR评价心肌组织和细胞microRNA-22、COL1A1mRNA、COL3A1mRNA表达情况,Western blot评价心肌组织和细胞TGFβ-1表达情况。结果 (1)心肌组织Masson染色显示红花-葶苈子药对抑制心肌梗死后心衰小鼠心肌纤维化,上调心肌组织microRNA-22表达、下调TGFβ-1表达。(2)细胞实验证实Ang II明显促进成纤维细胞及微血管内皮细胞增殖,上调成纤维细胞COL1A1、COL3A1、TGFβ-1表达,下调microRNA-22表达;过表达microRNA-22成纤维细胞其COL1A1、COL3A1、TGFβ-1表达水平明显下降;红花-葶苈子药对则可下调COL1A1、COL3A1、TGFβ-1表达,上调microRNA-22表达,抑制成纤维细胞增殖和胶原合成。结论红花-葶苈子药对抑制心肌梗死后心衰小鼠心肌纤维化,其机制与调节成纤维细胞miRNA-22/TGFβ-1信号通路表达有关。Objective To investigate the anti-fibrotic efficacy of drug pair of Honghua( Carthamus tinctorius L) and Tinglizi( Lepidium apetalum Willd) in a myocardial infarction-induced mice model of heart failure anddetermine its mechanism of action.Methods Forty C57 BL/6 male mice were selected and myocardial infarction was induced in mice by coronary artery ligation.Cardiac fibroblasts( CFs) and cardiac microvascular endothelial cells( CMECs) were isolated from C57 BL/6 male mice,and Ang II was used to induce excessive cell proliferation and collagen synthesis.Histological examination was carried out to estimate the degree of myocardial fibrosis.Expressions of microRNA-22,COL1 A1 mRNA and COL3 A1 mRNA was measured by Real time-PCR and TGFβ-1 was measured by Western blot in cardiac tissue and CFs.Results(1)Histopathological changes showed that drug pair of Honghua( Carthamus tinctorius L) and Tinglizi( Lepidium apetalum Willd) inhibited myocardial fibrosis in heart failure mice.Treatment with drug pair of Honghua( Carthamus tinctorius L) and Tinglizi( Lepidium apetalum Willd) up-regulated microRNA-22 expression in heart tissue,and down-regulated TGFβ-1 expression.(2)Cell experiments confirmed that Ang II promoted CFs and CMECs cell proliferationand CFs collagen synthesis.Ang II up-regulated expressions of COL1 A1,COL3 A1 and TGFβ-1 and down-regulated microRNA-22 expression on CFs.Over-expression microRNA-22 CFs showed lower expressions of COL1 A1,COL3 A1 and TGFβ-1.Drug pair of Honghua( Carthamus tinctorius L) and Tinglizi( Lepidium apetalum Willd) up-regulated expressions of COL1 A1,COL3 A1 and TGFβ-1 and down-regulated microRNA-22 expression.Conclusion The drug pair of Honghua( Carthamus tinctorius L) and Tinglizi( Lepidium apetalum Willd) inhibits myocardial fibrosis in post-myocardial infarction heart failure mice by regulating the microRNA-22/TGFβ-1 pathway in CFs.

关 键 词：红花 葶苈子 药对 心肌纤维化 microRNA 

分 类 号：R285[医药卫生—中药学]