Regulation Mechanism of AMPK/PGC-1α Pathway on Cardiac Injury and Mitochondrial Energy Metabolism in Rats with Uremic Cardiomyopathy
Objective To investigate the regulatory mechanism of AMP-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor gamma coactivator Ⅰ alpha(PGC-1α)pathway on heart injury and mitochondrial energy metabolism in rats with uremic cardiomyopathy(UCM).Methods Thirty rats were randomly divided into three groups:control group,UCM group and doxorubicin(DOX)group,with 10 rats in each group.Left ventricular ejection fraction(LVEF),left ventricular internal-diastolic dimension(LVIDD)and E/A were measured by echocardiography.HE staining was used to detect the pathological changes of myocardial tissue.Masson staining was used to detect myocardial fibrosis.Western blotting was used to detect the protein levels of AMPK,PGC-1α,phosphorylated AMPK(p-AMPK)and p-PGC-1α in myocardial tissue.Mitochondrial membrane potential was measured by JC-1 kit.The activity of mitochondrial respiratory chain complex Ⅰ～Ⅴ was detected by mitochondrial respiratory chain complex Ⅰ～Ⅴ kit.ATP level was detected by ATP content detection kit.The ultrastructure of myocardial mitochondria was detected by transmission electron microscope.Results Compared with the control group,the myocardium fibers in UCM group were disorganized and broken,and a large amount of collagen could be seen in the myocardium space.There was no significant difference in LVEF,LVIDD increased,E/A decreased(P＜0.05),there was no significant difference in the expression of AMPK and PGC-1α in myocardial tissue,while the expression of p-AMPK and p-PGC-1α increased(P＜0.05),myocardial mitochondria were swollen and vacuolated,some mitochondrial cristae disappeared,mitochondrial membrane potential decreased,ATP content decreased(P＜0.05),the activities of myocardial mitochondrial respiratory chain complex Ⅰ～Ⅴ were decreased(P＜0.05).Compared with UCM group,myocardial fiber injury was improved,collagen deposition in myocardial space was reduced,LVEF was not significantly different,LV1DD was decreased,E/A was increased(P＜0.05),there was no significant difference in the expression of AMPK and PGC-1αin myocardial tissue,and the expression of p-AMPK and p-PGC-1α decreased(P＜0.05),myocardial mitochondrial structure improved,mitochondrial membrane potential increased,ATP content increased(P＜0.05),the activities of myocardial mitochondrial respiratory chain complex Ⅰ～Ⅴ were increased(P＜0.05)in DOX group.Conclusion Inhibition of AMPK/PGC-lα pathway phosphorylation can improve cardiac function and myocardial histopathological changes in UCM rats,improve mitochondria and explore mitochondrial energy metabolism.
Uremic cardiomyopathyAMPK/PGC-1α pathwayMitochondrial energy metabolism
NETL
NSTL
万方数据
