Effect of Yiqi Wenyang Huoxue Lishui Components on Cardiac Function and Mitochondrial Energy Metabolism in CHF Rats
Objective:To investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure(CHF)and explore the underlying mechanism.Methods:The rat model of CHF was prepared by transverse aortic constriction(TAC).Eight of the 50 SD rats were randomly selected as the sham group,and the remaining 42 underwent TAC surgery.The 24 SD rats successfully modeled were randomized into model,trimetazidine(6.3 mg·kg-1),and Yiqi Wenyang Huoxue Lishui components(60 mg·kg-1 total saponins of Astragali Radix,10 mg·kg-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma,190 mg·kg-1 aqueous extract of Lepidii Semen,and 100 mg·kg-1 cinnamaldehyde)groups.The rats were administrated with corresponding agents by gavage,and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg-1 for 8 weeks.Echocardiography was used to examine the cardiac function in rats.Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide(NT-ProBNP),hypersensitive troponin(cTnⅠ),creatine kinase(CK),lactate dehydrogenase(LD),free fatty acids(FFA),superoxide dismutase(SOD),and malondialdehyde(MDA).The colorimetric assay was employed to measure the levels of adenosine triphosphate(ATP),adenosine diphosphate(ADP),and adenosine monophosphate(AMP)in the myocardial tissue.The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining.The Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in the myocardial tissue were determined by the colorimetric assay.The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy.Western blot was employed to determine the protein levels of ATP synthase subunit delta(ATP5D),glucose transporter 4(GLUT4),and carnitine palmitoyltransferase-1(CPT-1).The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ,Ⅱ,Ⅲ,and Ⅳ.Results:Compared with the sham group,the model group showed a loosening arrangement of cardiac fibers,fracture and necrosis of partial cardiac fibers,inflammatory cells in necrotic areas,massive blue fibrotic tissue in the myocardial interstitium,increased collagen fiber area and myocardial fibrosis,destroyed mitochondria,myofibril disarrangement,sparse myofilaments,and fractured and reduced cristae.In addition,the rats in the model group showed declined ejection fraction(EF)and fractional shortening(FS),risen left ventricular end-diastolic diameter(LVIDd),left ventricular end-systolic diameter(LVIDs),left ventricular end-diastolic posterior wall thickness(LVPWd),left ventricular end-systolic posterior wall thickness(LVPWs),left ventricular end-diastolic volume(LVVOLd),and left ventricular end-systolic volume(LVVOLs),elevated levels of NT-ProBNP,cTnⅠ,CK,MDA,FFA,and LD,lowered level of SOD,down-regulated protein levels of GLUT4 and CPT-1,decreased activities of Na+-K+-ATPase,Ca2+-Mg2+-ATPase,and respiratory complexes Ⅰ-Ⅳ,and declined levels ofATP5D,ATP,ADP,and AMP(P＜0.05,P＜0.01).Compared with the model group,the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue,risen EF and FS,declined LVIDd,LVIDs,LVPWd,LVPWs,LVVOLd,and LVVOLs,lowered levels of NT-ProBNP,cTnⅠ,CK,MDA,FFA,and LD,elevated level of SOD,up-regulated protein levels of GLUT4 and CPT-1,increased activities of Na+-K+-ATPase,Ca2+-Mg2+-ATPase,and respiratory complexes Ⅰ-Ⅳ,and elevated levels ofATP5D,ATP,ADP,and AMP(P＜0.05,P＜0.01).Conclusion:Yiqi Wenyang Huoxue Lishui components can improve the cardiac function,reduce myocardial injury,regulate glucose and lipid metabolism,optimize the utilization of substrates,and alleviate the damage of mitochondrial structure and function,thus improving the energy metabolism of the myocardium in the rat model of CHF.
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