The Mechanism of Lipoxin A4 Alleviating Myocardial Ischemia/Reperfusion Injury by Inhibiting Ferroptosis
WU Lingzhi
YANG Qian
LIU Sunli
HAO Dajie
MI Xiaolong
ZHU Kaiyi
Abstract:Objective:To explore the cardiac protective effect of lipoxin A4 liposome(LXA4)on myocardial ischemia/reperfusion(I/R)injury in rats,especially its influence on ferroptosis of cardiomyocytes.Methods:The myocardial I/R injury model was established using male Sprague-Dawley(SD)rats and randomly divided into the control group,the LXA4 group,the I/R group,and the I/R+LXA4 group.The effects of LXA4 on related markers such as myocardial structure,myocardial inflammatory response,oxidative stress and ferric death were evaluated by hematoxylin-eosin(HE)staining,Prussian blue(Perls)staining,Western Blot and real-time polymerase chain reaction(RT-PCR).Results:LXA4 significantly alleviated myocardial structural injury and myocardial inflammatory response induced by I/R.LXA4 also enhanced the activities of glutathione(GSH),catalase(CAT),and superoxide dismutase(SOD).lt inhibited the abnormal expressions of ferroptose-related protein solate carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),gene iron response element binding protein 2(IREB2),ATP synthase F0 complex subunit C3(ATP5G3),etc.,and reduced the occurrence of ferroptosis in cardiomyocytes.Conclusion:LXA4 may alleviate myocardial I/R injury and exert its cardiac protective effect by inhibiting ferroptosis of myocardial cells and enhancing the antioxidant and anti-inflammatory capabilities of the myocardium.As a new endogenous compound,LXA4 not only serves as an effective drug for the prevention and treatment of myocardial I/R injury,but also may exert potential effect in diseases related ferroptosis of cardiomyocytes.
Keywords:myocardial ischemia/reperfusion injurylipoxin A4ferroptosisexperimental study
Publication Date:2025-07-10
Online Publishing Date:2025-08-15(First online date of this platform, not the publication date of the document)
Pages:8( 1971-1978 )