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心阴片作用机制的生物技术阐释:SIRT1激活通过抑制内皮-间充质转化减轻心脏纤维化

Biotechnological Elucidation of Xinyin Tablet's Mechanism: SIRT1 Activation Attenuates Cardiac Fibrosis Via Suppressing Endothelial-to-Mesenchymal Transition.

作者信息

Li Qiao, Ye Taochun, Chu Qingmin, Shang Xin, Liu Min

机构信息

The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

Department of Endocrinology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, 510405, China.

出版信息

Iran J Biotechnol. 2025 Apr 1;23(2):e4086. doi: 10.30498/ijb.2025.510746.4086. eCollection 2025 Apr.

DOI:10.30498/ijb.2025.510746.4086
PMID:40860048
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12374124/
Abstract

BACKGROUND

Xinyin tablet (XYT), a traditional Chinese medicine consisting of , , , , , and other medicines, is clinically used to manage chronic heart failure (HF), yet its molecular mechanisms remain underexplored.

OBJECTIVES

This study integrates biotechnological approaches to investigate how XYT mitigates cardiac fibrosis by targeting the SIRT1-mediated TGF-β/Smad signaling pathway.

MATERIALS AND METHODS

Transverse aortic constriction (TAC)-induced HF mice and TGF-β1-stimulated myocardial microvascular endothelial cells (MMECs) were employed. Echocardiography, histopathology, and molecular assays (qRT-PCR, Western blotting, siRNA transfection) were utilized to assess cardiac function, fibrosis, and signaling pathways.

RESULTS

XYT treatment significantly improved cardiac function (↑LVEF, LVFS; ↓LVIDs, LVIDd) and reduced collagen I/III deposition in TAC mice. Mechanistically, XYT upregulated SIRT1 expression while suppressing EndMT markers (↓α-SMA, ↑VE-cadherin) and TGF-β/Smad signaling (↓TGF-βR1, p-Smad2/3). Crucially, SIRT1 knockdown in MMECs abolished XYT's inhibitory effects on EndMT and TGF-β/Smad activation, confirming SIRT1's pivotal role.

CONCLUSIONS

These findings highlight XYT's biotechnological relevance by linking SIRT1 activation to EndMT inhibition, offering a novel therapeutic strategy for cardiac fibrosis. This study underscores the potential of integrating traditional medicine with molecular biotechnology to develop targeted therapies for cardiovascular diseases.

摘要

背景

心阴片(XYT)是一种由[具体成分]等组成的中药,临床上用于治疗慢性心力衰竭(HF),但其分子机制仍未得到充分探索。

目的

本研究整合生物技术方法,以研究心阴片如何通过靶向沉默调节蛋白1(SIRT1)介导的转化生长因子-β(TGF-β)/Smad信号通路减轻心脏纤维化。

材料与方法

采用横向主动脉缩窄(TAC)诱导的HF小鼠和TGF-β1刺激的心肌微血管内皮细胞(MMECs)。利用超声心动图、组织病理学和分子检测(qRT-PCR、蛋白质免疫印迹法、小干扰RNA转染)评估心脏功能、纤维化和信号通路。

结果

心阴片治疗显著改善了TAC小鼠的心脏功能(左心室射血分数↑、左心室短轴缩短率↑;左心室舒张末期内径↓、左心室收缩末期内径↓),并减少了I/III型胶原蛋白沉积。机制上,心阴片上调SIRT1表达,同时抑制内皮-间质转化标志物(α-平滑肌肌动蛋白↓、血管内皮钙黏蛋白↑)和TGF-β/Smad信号(TGF-β受体1↓、磷酸化Smad2/3↓)。至关重要的是,MMECs中SIRT1基因敲低消除了心阴片对内皮-间质转化和TGF-β/Smad激活的抑制作用,证实了SIRT1的关键作用。

结论

这些发现通过将SIRT1激活与内皮-间质转化抑制联系起来,突出了心阴片的生物技术相关性,为心脏纤维化提供了一种新的治疗策略。本研究强调了将传统医学与分子生物技术相结合以开发心血管疾病靶向治疗方法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523d/12374124/c6ce6a0a8c9a/IJB-23-2-e4086-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523d/12374124/56041237c2db/IJB-23-2-e4086-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523d/12374124/b06fbb6b4af3/IJB-23-2-e4086-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523d/12374124/9a7c9c8d4502/IJB-23-2-e4086-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523d/12374124/c6ce6a0a8c9a/IJB-23-2-e4086-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523d/12374124/56041237c2db/IJB-23-2-e4086-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523d/12374124/b06fbb6b4af3/IJB-23-2-e4086-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523d/12374124/9a7c9c8d4502/IJB-23-2-e4086-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523d/12374124/c6ce6a0a8c9a/IJB-23-2-e4086-g004.jpg

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