Effects of FNDC5 Overexpression on Oxidative Stress and Apoptosis in Aged Rats with Chronic Heart Failure
Kongbati·Shatibieke
ZHAI Hui
WANG Ning
WANG Hong
Abstract：Objective:To investigate the effects of type Ⅲ fibronectin domain protein 5(FNDC5)overexpression on oxidative stress,apoptosis,and adenylate-activated protein kinase(AMPK)/silencing information regulatory factor 1(SIRT1)signaling pathway in aged rats with chronic heart failure(CHF).Methods:The elderly CHF rat model was established by intraperitoneal injection of Adriamycin,the successful constructed elderly CHF rats were randomly divided into model group(CHF group),empty lentivirus group(Lv-NC group),FNDC5 overexpression lentivirus group(Lv-FNDC5 group),FNDC5 overexpression lentivirus+AMPK inhibitor Compound C group(Lv-FNDC5+Compound C group),with 10 rats in each group.Ten normal aged rats were used as blank control group(Control group).Cardiac function parameters[left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD)]were detected by echocardiography.The pathological morphology of myocardium was observed by hematoxylin-eosin(HE)staining.The levels of oxidative stress indexes[superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA)]in myocardial tissue were detected by kit method.The apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL)staining.The expression of FNDC5 gene was detected by qRT-PCR;The expression of FNDC5 protein and AMPK/SIRT1 signaling pathway protein were detected by Western Blot.Results:Compared with the Control group,the myocardial tissue of CHF group showed obvious interstitial edema and focal cytoplasmic vacuoles,with a large number of inflammatory cell infiltration.Compared with the CHF group,the pathological damage of myocardium in the Lv-FNDC5 group was significantly alleviated.Compared with the Lv-FNDC5 group,the pathological damage of myocardium in the Lv-FNDC5+Compound C group was significantly aggravated.Compared with the Control group,the levels of LVEF and LVFS in CHF group were decreased,while the levels of LVESD and LVEDD were increased(P＜0.05);The activity of SOD and GSH-Px in myocardial tissue were decreased,while the content of MDA and apoptosis rate were increased(P＜0.05);The relative expression of FNDC5 mRNA and protein,p-AMPK/AMPK ratio,and the relative expression of SIRT1 protein in myocardial tissue were decreased(P＜0.05).Compared with the CHF group,the levels of LVEF and LVFS in Lv-FNDC5 group were increased,while the levels of LVESD and LVEDD were decreased(P＜0.05);The activity of SOD and GSH-Px in myocardial tissue were increased,while the content of MDA and apoptosis rate were decreased(P＜0.05);The relative expression of FNDC5 mRNA and protein,p-AMPK/AMPK ratio,and the relative expression of SIRT1 protein in myocardial tissue were increased(P＜0.05).Compared with the Lv-FNDC5 group,the levels of LVEF and LVFS in Lv-FNDC5+Compound C group were decreased,while the levels of LVESD and LVEDD were increased(P＜0.05);The activity of SOD and GSH-Px in myocardial tissue were decreased,while the content of MDA and apoptosis rate were increased(P＜0.05);The ratio of p-AMPK/AMPK and the relative expression of SIRT1 protein in myocardial tissue were decreased(P＜0.05).Conclusion:FNDC5 overexpression improves cardiac function in elderly CHF rats by reducing oxidative stress and apoptosis,and its mechanism may be related to the activation of AMPK/SIRT1 signaling pathway.
Keywords：chronic heart failuretype Ⅲ fibronectin domain protein 5oxidative stressapoptosisexperimental study
Publication Date：2025-02-15
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 378-386 )