Effect of Qihong Capsule on Myocardial Mitochondrial Energy Metabolism and AKT/AMPK-mTOR Signaling Pathway in Rats with Ischemic Heart Failure
Objective:To explore the effect of Qihong capsule on mitochondrial energy metabolism in rats with ischemic heart failure(IHF)and its regulatory mechanism.Methods:Thirty-six male sprague-dawley rats were randomly divided into sham operation group(n=6)and model group(n=30).The IHF model was prepared by ligation of the left anterior descending coronary artery.Sucessfully molded rats were randomly divided into 5 groups according to their body weight:model group,positive drug group,low-dose Qihong capsule group[QH-L,0.324 g/(kg·d)],medium-dose Qihong capsule group[QH-M,0.648 g/(kg·d),high-dose Qihong capsule group[QH-H,1.296 g/(kg·d)],the rats in sham operation group and model group were given the same volume of normal saline(10 mL/kg)by gavage once a day.After four weeks of continuous intervention,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF)and fractional shortening of short axis(FS)were measured by M-mode ultrasound to determine the structure and function of the heart.Deoxyribonucleotide end transferase mediated notch end labeling(TUNEL)staining was used to observe the pathological morphology of myocardial tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum glucose(Glu),lactate(LD),ketone bodies(KB),and free fatty acids(FFA).Mitochondrial permeability transition pore(mPTP)detection kit was used to detect the fluorescence intensity.Mitochondrial membrane potential detection kit(JC-1 method)was used to detect mitochondrial membrane potential.MitoSOXTM Red mitochondrial superoxide indicator was used to detect the content of reactive oxygen species(ROS),and Western Blot was used to detect the protein expression of protein kinase B(AKT),AMP-activated protein kinase(AMPK),and mammalian target of rapamycin(mTOR)in the myocardium.Results:Compared with sham operation group,LVEDD,LVESD,apoptosis rate,Glu,LD,FFA,KB,mitochondrial membrane potential,ROS,phosphorylated AMPK(p-AMPK)protein expression levels increased in model group(P<0.05).The expression levels of LVEF,FS,mPTP,phosphorylated AKT(p-AKT),and phosphorylated mTOR(p-mTOR)decreased(P<0.05).Compared with model group,the levels of Glu,LD,FFA,KB,mitochondrial membrane potential,and ROS in QH-L group,QH-M group,QH-H group,and positive drug group significantly decreased(P<0.05),and the expression levels of mitochondrial mPTP and p-AKT significantly increased(P<0.05).The LVEDD,apoptosis rate,and p-AMPK in QH-M group and QH-H group significantly decreased(P<0.05),while LVEF and FS significantly increased(P<0.05).Compared with QH-L group,the levels of LVEF,FS,LD,mitochondrial mPTP and p-AKT in QH-H group and positive drug group significantly increased,while the expression levels of LVESD,ROS and p-AMPK decreased(P<0.05).Compared with QH-L group,the levels of LVEF,FS,mitochondrial mPTP,and p-AKT in QH-H group and positive drug group significantly increased,while the expression levels of LVESD,ROS and p-AMPK decreased(P<0.05).Conclusion:Qihong capsule can regulate the process of myocardial metabolic substrate in IHF rats,reduce the over-production of ROS,protect the function of mitochondria,activate AKT to up-regulate the activity of mTOR,inhibit the apoptosis and alleviate the injury of myocardial cells,the mechanism of myocardial protection by regulating energy metabolism may be related to the expression of AKT/AMPK-mTOR signaling pathway protein.
ischemic heart failureQihong capsuleenergy metabolismmitochondrial dysfunctionprotein kinase B/AMP-activated protein kinase-mammalian target of rapamycin signaling pathway
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