Effect of semaglutide on myocardial injury induced by coronary microembolization in rats via regulation of the AMPK/NLRP3 signaling pathway
10.19405/j.cnki.issn1000-1492.2026.08.012
- VernacularTitle:司美格鲁肽调节AMPK/NLRP3信号通路对大鼠冠状动脉微栓塞致心肌损伤的影响
- Author:
Yangchun LIU
1
;
Huafeng YANG
1
;
Wanzhong HUANG
2
;
Yuan HUANG
2
;
Qiang SU
2
Author Information
1. Cardiothoracic Surgery Intensive Care Unit， The First Affiliated Hospital of Guangxi Medical University， Nanning 530021
2. Department of Cardiology， Jiangbin Hospital of Guangxi Autonomous Zhuang Region， Nanning 530021
- Publication Type:Journal Article
- Keywords:
coronary microembolization;
semaglutide;
myocardial injury;
pyroptosis;
AMPK/NLRP3 signaling pathway
- From:
Acta Universitatis Medicinalis Anhui
2026;61(8):1424-1430
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect of semaglutide （SEM） on myocardial injury induced by coronary microembolization （CME） in rats via the adenosine monophosphate-activated protein kinase （AMPK）/nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） signaling pathway. MethodsThirty-two rats were randomly assigned to four groups （n=8）： the Sham group， the CME group， the CME + SEM group， and the CME + SEM + Compound C （CC， a specific inhibitor of AMPK） group. The CME model was established by injecting microembolic spheres into the left ventricle， while the Sham group received an equal volume of normal saline via left ventricular injection. The CME + SEM group received subcutaneous injections of SEM （1 mg/kg， once weekly） for 4 weeks before CME induction. For the CME + SEM + CC group， rats were treated with SEM for 4 weeks， followed by an intravenous injection of CC （0.25 mg/kg dissolved in sterile normal saline） 30 minutes before CME modeling. 24 hours post-modeling， all groups underwent the following assessments： echocardiography to evaluate cardiac function， HE staining for myocardial histopathological analysis， Heidenhain staining to quantify the microinfarct area， ELISA to determine serum cardiac troponin T （cTnT） levels， and Western blot analysis to detect the expression of proteins related to the AMPK/NLRP3 pathway in cardiac tissues. ResultsCompared with the Sham group， the CME group showed significantly deteriorated cardiac function， elevated serum cTnT levels， and a marked increase in myocardial microinfarct area （P<0.05）. Compared with the CME group， the CME + SEM group exhibited significant improvements in cardiac function， decreased cTnT levels， and a remarkable reduction in myocardial microinfarct area （P<0.05）. Histopathological analysis revealed a normal myocardial structure in the Sham group without infarction. In contrast， the CME group showed disorganized myocardial arrangement， accompanied by nuclear fragmentation and karyolysis. In the CME + SEM group， myocardial degeneration， edema and inflammatory cell infiltration were obviously alleviated. Compared with Sham group， the protein ratio of p-AMPK/AMPK slightly increased in the CME group， while the protein levels of NLRP3， gasdermin D-N domain （GSDMD-N）， apoptosis-associated speck-like protein containing a CARD （ASC）， caspase-1 p20， interleukin（IL）-1β ， and IL-18 were markedly upregulated （P<0.05）. Notably， compared to the CME group， the CME + SEM group had a further elevated p-AMPK/AMPK ratio， while the protein levels of NLRP3， GSDMD-N， ASC， caspase-1 p20， IL-1β and IL-18 were markedly decreased （P<0.05）. ConclusionSEM significantly ameliorates CME-induced myocardial injury， and its mechanism of action may be closely associated with promoting AMPK phosphorylation， inhibiting NLRP3 inflammasome-mediated inflammatory responses， and suppressing pyroptosis.
