Mechanisms of Shuangshen Ningxin Capsules in Modulating NF-κB and MAPK Signaling Pathways to Reduce Cardiac Inflammation and Alleviate Myocardial Ischemia-reperfusion Injury in Rats
10.13422/j.cnki.syfjx.20260402
- VernacularTitle:双参宁心胶囊调节NF-κB和MAPK信号通路减轻心脏炎症改善大鼠心肌缺血再灌注损伤及机制
- Author:
Shujuan XU
1
;
Gaojie XIN
2
;
Ce CAO
1
;
Zixin LIU
1
;
Yuanyuan CHEN
1
;
Ran ZHAO
1
;
Lu XING
1
;
Yehao ZHANG
1
;
Yue SHI
1
;
Yanlei MA
1
;
Jianhua FU
1
Author Information
1. Institute of Basic Medicine， Xiyuan Hospital， China Academy of Chinese Medical Sciences， Beijing 100091，China
2. College of Pharmaceutical Sciences， Zhejiang Chinese Medical University， Hangzhou 310053，China
- Publication Type:Journal Article
- Keywords:
Shuangshen Ningxin capsules;
myocardial ischemia-reperfusion injury （MIRI）;
cardiac inflammation;
nuclear factor-κB （NF-κB） signaling pathway;
mitogen-activated protein kinase （MAPK） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(23):83-91
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect and mechanism of Shuangshen Ningxin capsules （SSNX） in regulating the nuclear factor-κB （NF-κB） and mitogen-activated protein kinase （MAPK） pathways to inhibit inflammation and alleviate myocardial ischemia-reperfusion injury （MIRI） in rats. MethodsThe 45 healthy male Sprague-Dawley （SD） rats were divided into sham operation group， model group， and SSNX capsules group （90 mg·kg-1）. The left anterior descending coronary artery was ligated to establish the MIRI model. Cardiac function was evaluated by echocardiography， and microvascular reperfusion was analyzed using contrast echocardiography. Myocardial inflammation and injury were assessed by hematoxylin and eosin （HE） staining， immunohistochemistry， and TdT-mediated dUTP nick end labeling （TUNEL）. The expression levels of cardiac inflammatory cytokines， including interleukin-1α （IL-1α）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Core differentially expressed genes （DEGs） and enriched pathways were screened by transcriptome sequencing. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to verify the mRNA expression of Toll-like receptor 2 （TLR2）， chemokine （C-X-C motif） ligand 1 （CXCL1） and prostaglandin-endoperoxide synthase 2 （PTGS2）， as well as the protein expression of Caspase-3， cleaved Caspase-3， p-NF-κB/NF-κB， phosphorylated extracellular signal-regulated kinase 1/2 （p-ERK1/2/ERK1/2） and p-p38 MAPK/p38 MAPK. ResultsCompared with the sham operation group， the ejection fraction （EF）， fractional shortening （FS）， stroke volume （SV） and cardiac output （CO） of the model group were significantly decreased （P<0.01）， the peak time of myocardial perfusion was prolonged （P<0.01）， hypoxia-inducible factor （HIF）-1α and α-smooth muscle actin （SMA） expression increased （P<0.01）， the concentrations of inflammatory factors IL-1α， IL-6， TNF-α， TLR2， CXCL1 and PTGS2 increased （P<0.01）， and the expression of cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins was significantly increased （P<0.01）. SSNX could improve cardiac function （P<0.05， P<0.01）， and significantly shorten the peak time of myocardial perfusion （P<0.01）. Moreover， it could also down-regulate HIF-1α and a-SMA expression （P<0.05， P<0.01）， and reduce the concentrations of IL-1α， IL-6， TNF-α （P<0.01）， and the mRNA expression of TLR2， CXCL1 and PTGS2 （P<0.01）. Additionally， SSNX inhibited the apoptosis rate （P<0.01） and significantly reduced the expression of Cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins （P<0.01）. ConclusionSSNX can alleviate cardiac inflammation by regulating the NF-κB and MAPK signaling pathways， thereby effectively preventing and alleviating myocardial reperfusion injury.
