Guanxinning injection ameliorates cardiac remodeling in HF mouse and 3D heart spheroid models via p38/FOS/MMP1-mediated inhibition of myocardial hypertrophy and fibrosis

被引：9

作者：

Fan, Siwen ^{[1
,2
]}

Xiao, Guangxu ^{[1
,2
]}

Ni, Jingyu ^{[1
,2
,3
]}

Zhao, Yuhan ^{[1
,2
]}

Du, Hongying ^{[1
,2
]}

Liang, Yingran ^{[1
,2
]}

Lv, Ming ^{[1
,2
]}

He, Shuang ^{[1
,2
]}

Fan, Guanwei ^{[1
,2
,3
]}

Zhu, Yan ^{[1
,2
]}

机构：

[1] Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Chinese Med, Beihua South Rd, Tianjin 301617, Peoples R China

[2] Tianjin Univ Tradit Chinese Med, Tianjin Haihe Lab Modern Chinese Med, Beihua South Rd, Tianjin 301617, Peoples R China

[3] Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Tianjin Key Lab Translat Res TCM Prescript & Syndr, Tianjin 300193, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2023年 / 162卷

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

Guanxinning injection; Heart failure; Cardiac spheroids; Cardiac remodeling; FOS; IL-17A signaling pathway; VENTRICULAR PRESSURE-OVERLOAD; XIN-NING INJECTION; EXPRESSION; FAILURE; FOS; CONSTITUENTS; MORPHINE; THERAPY; PATHWAY;

D O I：

10.1016/j.biopha.2023.114642

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: Heart failure (HF) is a cardiovascular disease with high morbidity and mortality. Guanxinning injection (GXNI) is clinically used for the treatment of coronary heart disease, but its therapeutic efficacy and potential mechanism for HF are poorly understood. This study aimed to evaluate the therapeutic potential of GXNI on HF, with a special focus on its role in myocardial remodeling. Methods: 3D cardiac organoids and transverse aortic constriction (TAC) mouse models were established and utilized. Heart function and pathology were evaluated by echocardiography, hemodynamic examination, tailcuff blood pressure and histopathology. Key targets and pathways regulated by GXNI in HF mouse heart were revealed via RNA-seq and network pharmacology analysis, and were verified by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. Results: GXNI significantly inhibited cardiac hypertrophy and cells death. It protected mitochondrial function in cardiac hypertrophic organoids and markedly improved cardiac function in HF mice. Analysis of GXNI-regulated genes in HF mouse hearts revealed that IL-17A signaling in fibroblasts and the corresponding p38/c-Fos/Mmp1 pathway prominently mediated cardiac. Altered expressions of c-Fos, p38 and Mmp1 by GXNI in heart tissues and in cardiac organoids were validated by RT-PCR, WB, IHC, and IF. H&E and Masson staining confirmed that GXNI substantially ameliorated myocardial hypertrophy and fibrosis in HF mice and in 3D organoids. Conclusion: GXNI inhibited cardiac fibrosis and hypertrophy mainly via down-regulating p38/c-Fos/Mmp1 pathway, thereby ameliorating cardiac remodeling in HF mice. Findings in this study provide a new strategy for the clinical application of GXNI in the treatment of heart failure.

引用

页数：16