Qifu Qiangxin Decoction Regulates Notch1 and TGF-β 1/Smad Pathway Against Myocardial Fibrosis in Heart Failure
10.16466/j.issn1005-5509.2025.08.001
- VernacularTitle:芪附强心方调控Notch1及TGF-β1/Smad通路抗心力衰竭心肌纤维化
- Author:
Wei QIU
1
;
Yunyan ZHANG
;
Haoxuan DENG
Author Information
1. 浙江中医药大学第二临床医学院 杭州 310053
- Publication Type:Journal Article
- Keywords:
Qifu Qiangxin Decoction;
heart failure;
myocardial fibrosis;
Notch1;
TGF-β1/Smad pathway;
myocardial infarction;
cardiac fibroblasts;
Smad protein
- From:
Journal of Zhejiang Chinese Medical University
2025;49(8):935-947,967
- CountryChina
- Language:Chinese
-
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.
