浙江中医药大学学报2025，Vol.49Issue(8)：935-947,967,14.DOI:10.16466/j.issn1005-5509.2025.08.001
芪附强心方调控Notch1及TGF-β1/Smad通路抗心力衰竭心肌纤维化
Qifu Qiangxin Decoction Regulates Notch1 and TGF-β 1/Smad Pathway Against Myocardial Fibrosis in Heart Failure
摘要
Abstract
[Objective]To investigate the effect of Qifu Qiangxin Decoction on heart failure(HF)and explore its mechanism.[Methods]Forty male C57BL/6N mice were randomly divided into sham surgery(Sham)group,model(HF)group,low-dose Qifu Qiangxin Formula(HF+QL)group,high-dose Qifu Qiangxin Formula(HF+QH)group and angiotensin-converting enzyme inhibitor(HF+ACEI)group according to the random number table method.The mouse HF model was established by ligating the left anterior descending(LAD)artery.Cell model in cardiac fibroblasts(CFs)was stimulated by Angiotensin Ⅱ(Ang Ⅱ).Ang Ⅱ-stimulated CFs were treated with drug-containing serum or blank serum,then incubated with gamma-secretase inhibitor(DAPT)and transmembrane receptor Notch1 siRNA.Enzyme-linked immunosorbent assay(ELISA)was used to assess serum B-syndrome natriuretic peptide(BNP)levels in mice.Left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),ejection fraction(EF)and fraction shorting(FS)were measured by ultrasound cardiogram(UCG).The histological structure was observed after hematoxylin-eosin(HE)staining,while the collagen protein expression in heart muscle tissues was measured by using Picro sirius red(PSR)and Masson staining.Quantitative reverse transcription-polymerase chain reaction(qRT-PCR),western blot and immunofluorescence(IF)was used to determine the expression levels of collagenⅠ,collagen Ⅲ,α-smooth muscle actin(α-SMA),Notch1,Notch intracellular domain-1(NICD1),transforming growth factor-β1(TGF-β1),Smad protein 2(Smad2),phosphorylated-Smad2(p-Smad2),Smad protein 3(Smad3),phosphorylated-Smad3(p-Smad3),Smad protein 7(Smad7)in CFs and heart tissues,and the migration of CFs was determined by examining wound healing.[Results]Compared with HF group,Qifu Qiangxin Decoction reduced histopathological changes,serum BNP levels,LVESD and LVEDD,and collagen deposition,while increasing EF and FS(P<0.01,P<0.001).Qifu Qiangxin Decoction also notably inhibited the cell viability,migration,collagen Ⅰ,collagen Ⅲ mRNA and α-SMA protein expression in Ang Ⅱ stimulated CFs(P<0.05,P<0.01,P<0.001);promoted Notch1,NICD1 and Smad7 protein expression and hindered TGF-β1,p-Smad2,p-Smad3 protein expression in HF mice and Ang Ⅱ-stimulated CFs(P<0.001).siNotch1 abolished the impact of Qifu Qiangxin Decoction on Notch1,NICD1,TGF-β1,p-Smad2 and p-Smad3 protein expression,and cell viability,migration,as well as collagen Ⅰ,collagen Ⅲ mRNA and α-SMA protein expression in Ang Ⅱ-stimulated CFs(P<0.05,P<0.01,P<0.001).[Conclusion]To some extent,Qifu Qiangxin Decoction showed protective properties against HF,and its mechanism may be through the regulation of the TGF-β1/Smad pathway by Notch1.关键词
芪附强心方/心力衰竭/心肌纤维化/Notch1/TGF-β1/Smad通路/心肌梗死/心肌成纤维细胞/Smad蛋白Key words
Qifu Qiangxin Decoction/heart failure/myocardial fibrosis/Notch1/TGF-β1/Smad pathway/myocardial infarction/cardiac fibroblasts/Smad protein分类
医药卫生引用本文复制引用
邱渭,张云燕,邓浩轩,华军益..芪附强心方调控Notch1及TGF-β1/Smad通路抗心力衰竭心肌纤维化[J].浙江中医药大学学报,2025,49(8):935-947,967,14.基金项目
浙江省中医药管理局重点研究项目(2022ZZ018) （2022ZZ018）
2021年浙江中医药大学附属医院科研专项(2021FSYYZZ12) （2021FSYYZZ12）
衢州市科技攻关项目第二批中医药专项(2022K114) （2022K114）
2023年度衢州市市级科技攻关项目(2023K158)Key Research Project of Zhejiang Administration of Traditional Chinese Medicine(2022ZZ018) （2023K158）
2021 Affiliated Hospital Scientific Research Project of Zhejiang Chinese Medical University(2021FSYYZZ12) （2021FSYYZZ12）
The Second Batch of Traditional Chinese Medicine Special Projects of Quzhou Science and Technology Research Project(2022K114) （2022K114）
2023 Quzhou Municipal Science and Technology Research Project(2023K158) （2023K158）
