Impact of AMPKα on Myocardial Ischemia-reperfusion Oxidative Injury and Myocardial Fibers in Aged Rats and Its Mechanism
LI Jing
ZHANG Chenfeng
YU Li'na
XING Ying
ZHANG Ya'nan
SHI Jian
Abstract：Objective:To analyze the impact of adenylate-activated protein kinase(AMPK)α subunit(AMPKα)on myocardial ischemia-reperfusion(I/R)oxidative injury and myocardial fibers in aged rats,as well as its mechanism.Methods:The I/R injury models of clean-grade adult male SD rats and aged male SD rats were constructed.The experimental animals were divided into group A(young I/R),group B(aged I/R),group C(aged I/R+LV empty vector),and group D(aged I/R+AMPKα),with 10 rats in each group.Rats in group A and group B were not given other intervention before and after I/R.Rats in group C were transfected with the empty in plasmid vector pSuper immediately after reperfusion,and rats in group D were immediately transfected with recombinant plasmids containing AMPKα gene sequence-specific shRNA after reperfusion.The AMPKα mRNA and AMPKα protein expression in myocardial tissues,heart rate(HR),left ventricular ejection fraction(LVEF),serum myocardial injury markers,oxidative stress markers,hematoxylin and eosin(HE)staining and Masson staining of myocardial tissues,as well as the protein expression of fibrosis markers α-smooth muscle actin(α-SMA),transforming growth factor β(TGF-β),and fibronectin(FN)in 4 groups were compared.Results:Compared with group A,AMPKα mRNA,AMPKα protein,HR,LVEF and superoxide dismutase(SOD)significantly decreased,creatine kinase-MB(CK-MB),myoglob(Mb),cardiac troponin Ⅰ(cTnⅠ),lactate dehydrogenase(LDH),and malonaldehyde(MDA)significantly increased in group B(P≤0.05).Compared with group C,AMPKαmRNA,AMPKα protein,HR,LVEF,and SOD significantly increased,CK-MB,Mb,cTnⅠ,LDH,and MDA significantly decreased in group D(P＜0.05).Compared with group A,myocardial fibers were disordered,myocardial interstitial collagen fibers significantly increased,myocardial cell hypertrophy was more obvious,atrophy and vacuolar degeneration of myocardial cells were observed,and nuclei were more deeply stained in both group B and group C.Compared with group C,disorderly arrangement of myocardial fibers was alleviated,and myocardial interstitial collagen fibers,cardiomyocyte hypertrophy and deep staining nuclei reduced in group D.Compared with group A,the protein expression of α-SMA,TGF-β,and FN significantly increased in group B(P＜0.05).Compared with group C,the protein expression of α-SMA,TGF-β,and FN significantly decreased in group D(P＜0.05).Conclusion:Compared with young I/R rats,aged I/R rats shows more severe oxidative stress,myocardial injury,and fibrosis.Targeted up-regulation of the AMPKα subunit can effectively improve I/R injury in I/R rats.
Keywords：myocardial ischemia-reperfusionoxidative injurymyocardial fiberadenylate-activated protein kinase alpha subunitagedratexperimental 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：6( 1829-1834 )