Study on the Mechanism of Kukoamine A in Improving Myocardial Ischemia-reperfusion Injury via the AKT/GSK-3β Pathway
XU Han
DENG Long
ZHANG Guibin
CHEN Yongqing
WANG Weizu
CHEN Min
LIU Ling
SHI Fei
Abstract：objective:To investigate the possible effect of Kukoamine A(KuA)on myocardial ischemia-reperfusion(I/R)injury.Methods:Rats were randomly divided into the sham operation(Sham)group,the I/R group,the KuA 10 mg group,and the KuA 20 mg group.After 120 minutes of I/R treatment,left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),maximum rate of rise/decrease of left ventricular pressure(±dp/dtmax),and ischemic area were detected.The enzyme activities of catalase(CAT),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),as well as the levels of malondialdehyde(MDA),creatine kinase-MB(CK-MB)tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were detected using enzyme-linked immunosorbent assay(ELISA).Myocardial cell apoptosis was detected by terminal deoxy nucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The mRNA expression levels of glycogen synthase kinase 3β(GSK-3β)and protein kinase B(AKT)in mammalian myocardial tissue were detected by reverse transcription-polymerase chain reaction(RT-PCR).Results:Compared with other groups,the rats in the I/R group showed obvious oxidative stress and inflammatory responses.KuA can significantly improve myocardial function after I/R in a dose-dependent manner,which may be related to its effect on the activities of SOD and GSH-Px and the levels of MDA,IL-6,TNF-α,and L-1β in myocardial tissue.Conclusion:KuA can inhibit the gene expression of AKT/GSK-3β,reduce inflammation and oxidative stress responses after I/R,and improve I/R injury.
Keywords：myocardial ischemia-reperfusion injuryKukoamine Aprotein kinase B/target glycogen synthase kinase 3βoxidative stressexperimental study
Publication Date：2025-06-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 1805-1812 )