Nicorandil inhibits TLR4/MyD88/NF-κB/NLRP3 signaling pathway to reduce pyroptosis in rats with myocardial infarction.
Exp Biol Med (Maywood)
; 246(17): 1938-1947, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-34034564
Pyroptosis is an inflammatory cell death that regulates cardiomyocyte loss after myocardial infarction. Reports indicate that nicorandil has a strong anti-inflammatory effect and protects the myocardium from myocardial infarction. However, its relationship with pyroptosis is largely unreported. Here, we investigated to influence and mechanism of action of nicorandil on cardiomyocyte pyroptosis. Forty Sprague Dawley rats were randomly assigned to sham, MI, MI + nicorandil, and MI + nicorandil + TAK242 groups (10 per group). Myocardial infarction modeling was performed through ligation of the anterior descending branch of the left coronary artery. The function of cardiac was evaluated through echocardiography, detection of myocardial adenine nucleotides, cTnI, LDH, TTC, and HE staining. Moreover, we used qRT-PCR, immunohistochemistry, and Western blotting to examine the expression of pyroptosis-related molecules and the inflammasome pathway of TLR4/MyD88/NF-κB/NLRP3. Myocardial infarction caused the activation of GSDMD, aggravated myocardial injury, and triggered cardiac dysfunction. Myocardial infarction induced pyroptotic cell death, manifested as upregulation in mRNA and protein levels associated with pyroptosis, including caspase-1 cleavage and increased expression of IL-1ß and IL-18. These changes were mitigated by nicorandil. The achieved data implicate that myocardial infarction induces pyroptosis via the TLR4/MyD88/NF-κB/NLRP3 pathway, which can be inhibited by nicorandil pretreatment. Therefore, nicorandil exerts cardioprotective effects by activating KATP channels, and at least in part through inhibition of the TLR4/MyD88/NF-κB/NLRP3 pathway to reduce myocardial infarction-induced pyroptosis. As such, it is a potential therapy for ischemic heart disease.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nicorandil
/
Miocitos Cardíacos
/
Inflamasomas
/
Infarto del Miocardio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Exp Biol Med (Maywood)
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
/
MEDICINA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido