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Original Article

Korean J Physiol Pharmacol 2023; 27(2): 143-155

Published online March 1, 2023 https://doi.org/10.4196/kjpp.2023.27.2.143

Copyright © Korean J Physiol Pharmacol.

Resveratrol pretreatment alleviates NLRP3 inflammasome-mediated cardiomyocyte pyroptosis by targeting TLR4/MyD88/NF-κB signaling cascade in coronary microembolization-induced myocardial damage

Chang-Jun Luo1,2,#, Tao Li1,#, Hao-Liang Li1, You Zhou1, and Lang Li1,*

1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning 530021, 2Department of Cardiology, Affiliated Liutie Central Hospital of Guangxi Medical University, Liuzhou 545007, China

Correspondence to:Lang Li
E-mail: drlilang1968@126.com

#These authors contributed equally to this work.

Author contributions: C.L. and T.L. conceived and designed research. C.L. and T.L. conducted experiments. H.L. and Y.Z. contributed analytical tools. Y.Z. and L.L. analyzed data. C.L. and T.L. wrote the manuscript. All authors read and approved the manuscript.

Received: June 8, 2022; Revised: July 23, 2022; Accepted: July 26, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Percutaneous coronary intervention and acute coronary syndrome are both closely tied to the frequently occurring complication of coronary microembolization (CME). Resveratrol (RES) has been shown to have a substantial cardioprotective influence in a variety of cardiac diseases, though its function and potential mechanistic involvement in CME are still unclear. The forty Sprague–Dawley rats were divided into four groups randomly: CME, CME + RES (25 mg/kg), CME + RES (50 mg/kg), and sham (10 rats per group). The CME model was developed. Echocardiography, levels of myocardial injury markers in the serum, and histopathology of the myocardium were used to assess the function of the cardiac muscle. For the detection of the signaling of TLR4/MyD88/NF-κB along with the expression of pyroptosis-related molecules, ELISA, qRT-PCR, immunofluorescence, and Western blotting were used, among other techniques. The findings revealed that myocardial injury and pyroptosis occurred in the myocardium following CME, with a decreased function of cardiac, increased levels of serum myocardial injury markers, increased area of microinfarct, as well as a rise in the expression levels of pyroptosis-related molecules. In addition to this, pretreatment with resveratrol reduced the severity of myocardial injury after CME by improving cardiac dysfunction, decreasing serum myocardial injury markers, decreasing microinfarct area, and decreasing cardiomyocyte pyroptosis, primarily by blocking the signaling of TLR4/MyD88/NF-κB and also reducing the NLRP3 inflammasome activation. Resveratrol may be able to alleviate CME-induced myocardial pyroptosis and cardiac dysfunction by impeding the activation of NLRP3 inflammasome and the signaling pathway of TLR4/MyD88/NF-κB.

Keywords: Coronary microembolization, NLRP3, Pyroptosis, Resveratrol, TLR4/MyD88/NF-κB