Blocking RIPK2 Function Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating the AKT and NF-κB Pathways.
Immunol Invest
; 52(5): 529-545, 2023 Nov.
Article
en En
| MEDLINE
| ID: mdl-37128885
ABSTRACT
OBJECTIVE:
Inflammation and oxidation brought on by myocardial ischemia-reperfusion (MI/R) injury lead to cardiomyocyte apoptosis and necrosis. The receptor interacting serine/threonine kinase 2 (RIPK2) plays significant roles in oxidative stress and excessive inflammation. The purpose of this research is to examine the roles of RIPK2 in MI/R injury.METHODS:
The in vivo animal model was constructed by acute coronary I/R, and the in vitro cell model was established by oxygen and glucose deprivation/reperfusion (OGD/R)-stimulated cardiomyocyte injury. RIPK2 expression was examined using qRT-PCR and Western blot. CCK-8 was proposed as a method for detecting cell proliferation. ELISA was utilized to measure inflammatory cytokines (TNF-α, IL-6, and IL-1ß) and myocardial injury indicators (CK-MB, Mb, cTnI, and LDH). The levels of MDA and ROS were determined by the kit and fluorescent probe. H&E was conducted to assess MI/R injury after silencing of RIPK2.RESULTS:
In MI/R rats and OGD/R-treated H9C2 cardiomyocytes, RIPK2 was overexpressed at both the mRNA and protein levels. RIPK2 inhibition promoted cell proliferation while inhibiting apoptosis, as evidenced by decreased TUNEL-positive cells and cleaved caspase-3. RIPK2 inhibition reduced MDA and ROS levels, as well as the contents of inflammatory factors. RIPK2 silencing reduced CK-MB, Mb, cTnI, and LDH levels in rat serum and alleviated MI/R injury. Furthermore, RIPK2 inhibition increased p-AKT while decreasing NF-B p-p65 expression.CONCLUSION:
Silencing of RIPK2 reduced apoptosis, proinflammatory factors, and oxidative stress in MI/R by activating AKT and suppressing NF-κB signals, suggesting a potential therapeutic strategy for MI/R injury.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión Miocárdica
/
FN-kappa B
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2023
Tipo del documento:
Article