巴卡亭Ⅲ对心房纤维化的作用及其机制研究  

The effect of baccatin Ⅲ on atrial fibrosis and its mechanism

作　　者：陈龙[1] 方国建 唐东方 林雷[1] 蔡俊锋 周黎瑾[1] 许凌[1] 沈炜 刘洋 高文[1] CHEN Long;Fang Guojian;TANG Dongfang;LIN Lei;CAI Junfeng;ZHOU Lijin;XU Ling;SHEN Wei;LIU Yang;GAO Wen(Huadong Hospital Affiliated to Fudan University,Shanghai 200040,China;Xinhua Hospital Affiliated to School of Medicine,Shanghai Jiao Tong University,Shanghai 200092,China)

机构地区：[1]复旦大学附属华东医院,上海200040 [2]上海交通大学医学院附属新华医院,上海200092

出　　处：《宁波大学学报（理工版）》2022年第5期107-114,共8页Journal of Ningbo University：Natural Science and Engineering Edition

摘　　要：为探讨巴卡亭Ⅲ对心衰诱导的心房纤维化是否有效及潜在作用机制,本研究对C57BL/6小鼠行胸主动脉缩窄手术,构建心衰模型,进一步腹腔注射巴卡亭Ⅲ,以观察心房纤维化程度及相应信号通路的改变.在体外使用血管紧张素Ⅱ刺激成年小鼠心房成纤维细胞,巴卡亭Ⅲ处理后观察心房成纤维细胞分化、迁移和分泌细胞外基质的能力及TGF-β1/Smad2/3信号通路的改变.临床样本表明,心衰可以加重心房纤维化的程度(P<0.05).动物实验表明,巴卡亭Ⅲ可以减轻心衰诱导的小鼠心功能不全及左心房扩大和纤维化,并减轻心房组织TGF-β1/Smad2/3信号通路的激活(P<0.01).细胞实验表明,巴卡亭Ⅲ可以抑制Ang-Ⅱ所诱导的心房成纤维细胞分化、迁移和分泌细胞外基质的能力和减轻心房成纤维细胞TGF-β1/Smad2/3信号通路的激活(P<0.01).表明巴卡亭Ⅲ可通过TGF-β1/Smad2/3信号通路抑制心房成纤维细胞的活动,从而减轻心衰诱导的心房纤维化的发生发展.The current study was designed to investigate the effect and the underlying mechanism of baccatin Ⅲ on atrial fibrosis induced by heart failure. C57BL/6 mice were treated with thoracic aortic coarctation to establish the heart failure model. Baccatin Ⅲ was subsequently injected intraperitoneally to assess the degree of atrial fibrosis and the changes of corresponding signal pathway. Adult mouse atrial fibroblasts were stimulated with angiotensin Ⅱ in vitro and treated with baccatin Ⅲ to measure the ability of atrial fibroblasts to differentiate,migrate and secrete extracellular matrix and the changes of corresponding signal pathways. Clinical samples showed that heart failure aggravated the degree of atrial fibrosis. In addition, baccatine Ⅲ could reduce cardiac insufficiency, left atrial enlargement and fibrosis induced by heart failure in mice. TGF-β1/Smad2/3 signal pathway was activated in atrial tissue. Experimental results showed that baccatin Ⅲ could inhibit the differentiation, migration and secretion of extracellular matrix of atrial fibroblasts induced by Ang-Ⅱ and reduce the activation of TGF-β1/Smad2/3 signal pathway of atrial fibroblasts. Furthermore, baccatin Ⅲ inhibited the activity of atrial fibroblasts through TGF-β1/Smad2/3 signal pathway to reduce the occurrence and development of atrial fibrosis induced by heart failure.

关 键 词：心衰 心房颤动 心房纤维化 巴卡亭Ⅲ 

分 类 号：R541.75[医药卫生—心血管疾病]