巴卡亭III对心房纤维化的作用及其机制研究
PDF下载 (204)陈 龙,方国建,唐东方,林 雷,蔡俊锋,周黎瑾,许 凌,沈 炜,刘 洋,高 文.巴卡亭III对心房纤维化的作用及其机制研究[J].宁波大学学报(理工版),2022,35(5):107-114.DOI:
CHEN Long,Fang Guojian,TANG Dongfang,LIN Lei,CAI Junfeng,ZHOU Lijin,XU Ling,SHEN Wei,LIU Yang,GAO Wen.The effect of baccatin III on atrial fibrosis and its mechanism[J].Journal of Ningbo University(Natural Science & Engineering Edition),2022,35(5):107-114.DOI:
| Title: | The effect of baccatin III on atrial fibrosis and its mechanism |
| 作者: | 陈 龙, 方国建, 唐东方, 林 雷, 蔡俊锋, 周黎瑾, 许 凌, 沈 炜, 刘 洋, 高 文 |
| Author(s): | CHEN Long, Fang Guojian, TANG Dongfang, LIN Lei, CAI Junfeng, ZHOU Lijin, XU Ling, SHEN Wei, LIU Yang, GAO Wen |
| 关键词: | 心衰; 心房颤动; 心房纤维化; 巴卡亭III |
| Keywords: | heart failure, atrial fibrillation, atrial fibrosis, baccatin III |
| 分类号: | R541.7+5 |
| 文献标识码: | A |
| 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. |
| Abstract: | 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. |
| 参考文献 /References: | [1] 中华医学会心电生理和起搏分会, 中国医师协会心律学专业委员会, 中国房颤中心联盟心房颤动防治专家工作委员会. 心房颤动: 目前的认识和治疗建议(2021) [J]. 中华心律失常学杂志, 2022, 26(1):15-88. [2] Carlisle M A, Fudim M, DeVore A D, et al. Heart failure and atrial fibrillation, like fire and fury[J]. JACC Heart Failure, 2019, 7(6):447-456. [3] Mene-Afejuku T O, López P D, Akinlonu A, et al. Atrial fibrillation in patients with heart failure: Current state and future directions[J]. American Journal of Cardiovascular Drugs, 2018, 18(5):347-360. [4] Denham N C, Pearman C M, Caldwell J L, et al. Calcium in the pathophysiology of atrial fibrillation and heart failure[J]. Frontiers in Physiology, 2018, 9:1380. [5] Zhao N, Li Q, Zhang K, et al. Heart failure-induced atrial remodelling promotes electrical and conduction alternans [J]. PLoS Computational Biology, 2020, 16(7):e1008048. [6] Lee Y H, Lee Y R, Park C S, et al. Baccatin III, a precursor for the semisynthesis of paclitaxel, inhibits the accumulation and suppressive activity of myeloid-derived suppressor cells in tumor-bearing mice[J]. International Immunopharmacology, 2014, 21(2):487-493. [7] Lee Y H, Lee Y R, Kim K H, et al. Baccatin III, a synthetic precursor of taxol, enhances MHC-restricted antigen presentation in dendritic cells[J]. International Immunopharmacology, 2011, 11(8):985-991. [8] Nie Y, Zhang D, Qian F, et al. Baccatin III ameliorates bleomycin-induced pulmonary fibrosis via suppression of TGF-β1 production and TGF-β1-induced fibroblast differentiation[J]. International Immunopharmacology, 2019, 74:105696. [9] Song S, Liu L, Yu Y, et al. Inhibition of BRD4 attenuates transverse aortic constriction- and TGF-β-induced endothelial-mesenchymal transition and cardiac fibrosis [J]. Journal of Molecular and Cellular Cardiology, 2019, 127:83-96. [10] Song S, Zhang R, Mo B, et al. EZH2 as a novel therapeutic target for atrial fibrosis and atrial fibrillation [J]. Journal of Molecular and Cellular Cardiology, 2019, 135:119-133. [11] Wang Q, Yu Y, Zhang P, et al. The crucial role of activin A/ALK4 pathway in the pathogenesis of Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation[J]. Basic Research in Cardiology, 2017, 112(4):47. [12] Zhang Y, Qi Y, Li J J, et al. Stretch-induced sarcoplasmic reticulum calcium leak is causatively associated with atrial fibrillation in pressure-overloaded hearts[J]. Cardiovascular Research, 2020, 117(4):1091-1102. [13] Yamaguchi N, Xiao J, Narke D, et al. Cardiac pressure overload decreases ETV1 expression in the left atrium, contributing to atrial electrical and structural remodeling [J]. Circulation, 2021, 143(8):805-820. [14] Frangogiannis N G. Cardiac fibrosis: Cell biological mechanisms, molecular pathways and therapeutic opportunities[J]. Molecular Aspects of Medicine, 2019, 65:70-99. [15] Ge Z, Chen Y, Wang B, et al. MFGE8 attenuates Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation through inhibition of TGF-β1/Smad2/3 pathway[J]. Journal of Molecular and Cellular Cardiology, 2020, 139:164-175. [16] 全进伟, 吴立群, 谢玉才. 心房颤动与心力衰竭共存的病理机制[J]. 中华心律失常学杂志, 2021, 25(2):174-177. [17] 肖兴平, 薛竟宜, 李为民. 心力衰竭合并心房颤动与心房纤维化研究[J]. 国际心血管病杂志, 2012, 39(2):68- 70. [18] Hu C Y, Wang C Y, Li J Y, et al. Relationship between atrial fibrillation and heart failure[J]. European Review for Medical and Pharmacological Sciences, 2016, 20(21):4593-4600. [19] Burstein B, Nattel S. Atrial fibrosis: Mechanisms and clinical relevance in atrial fibrillation[J]. Journal of the American College of Cardiology, 2008, 51(8):802-809. [20] Sohns C, Marrouche N F. Atrial fibrillation and cardiac fibrosis[J]. European Heart Journal, 2020, 41(10):1123-1131. [21] 曹哲哲, 马瑞彦. 心房颤动的心房纤维化分子机制研究进展[J]. 心血管病学进展, 2019, 40(3):359-362. [22] Wang H, Liu M, Wang X, et al. MFAP4 deletion attenuates the progression of angiotensin II-induced atrial fibrosis and atrial fibrillation[J]. EP Europace, 2021, 24(2):340-347. |
| 备注/Memo: | 收稿日期: 2022－03－14. 宁波大学学报（理工版）网址: http://journallg.nbu.edu.cn/ 第一作者: 陈龙（1988－）, 男, 上海人, 主治医师/在读博士研究生, 主要研究方向: 房颤的发生机制. E-mail: heaven_long@126.com 宁波大学学报（理工版）网址：http://journallg.nbu.edu.cn/*通信作者: 高文（1960－）, 男, 上海人, 主任医师, 主要研究方向: 肺移植的临床和基础. E-mail: gaowen592121@163.com |
