| BackgroundThe China Cardiovascular Health and Disease Report 2021 shows that the burden of cardiovascular diseases continues to increase due to the dual effects of an aging population and the continuing prevalence of metabolic risk factors.From 1980 to 2019,the average annual growth rate of discharged patients with cardiovascular diseases in China was 9.59%,which was significantly faster than the average annual growth rate of discharged patients with all kinds of diseases in the same period(6.33%).The average annual growth rate of discharged patients with heart failure was the highest among all kinds of cardiovascular diseases(20.66%),and the 5-year all-cause mortality rate of heart failure reached 55.4%.The current treatment of heart failure is a combination of efficacy and adverse effects,and does not effectively reduce the risk of death.Traditional Chinese medicine has the advantages of good curative effect,individualization and low risk in treating heart failure,but its mechanism is not clear and needs to be explored.PurposeTo explore the relationship between heart failure and mitochondrial energy metabolism changes after myocardial infarction,verify the effect of Fuyang Qiangxin Decoction on improving mitochondrial function and alleviating myocardial hypertrophic,and further explore the mechanism of Fuyang Qiangxin Decoction on the metabolism of ketone body,the substrate of mitochondrial metabolism.MethodsThis study is divided into in vivo and in vitro experiments.In vivo experiments SD rats were selected for the ligation of the left anterior descending branch coronary artery.After 28 days of administration,echocardiography was performed to measure the ejection fraction,left ventricular shortening fraction,diastolic left ventricular diameter and systolic left ventricular diameter,so as to evaluate the changes in cardiac function of rats in each group after myocardial infarction.Blood was collected from abdominal aorta.Serum NT-proBNP content and β-hydroxybutyric acid content were detected,myocardial tissue was retained,hypertrophy related protein ANP,β-MHC content changes and myocardial ATP content were detected,and high-throughput sequencing was performed on the myocardium to screen the target and possible mechanism of Fuyang Qiangxin decoction.The morphological changes of myocardium were observed by HE staining,and the morphological and structural changes of myocardium mitochondria were further observed under transmission electron microscopy,so as to evaluate the effect of Fuyang Qiangxin Decoction on cardiac morphology and mitochondrial morphology and function.In vitro experiments,H9C2 cardiomyocytes were selected as the carrier,AngⅡwas used to induce the hypertrophy model,and Fuyang Qiangxin Decoction was administered with freeze-dried powder.Mitochondrial membrane potential changes of cardiomyocytes were detected,and the effect of Fuyang Qiangxin Decoction on early apoptosis was evaluated.Cell survival rate was observed by MTT assay,and ATP content changes in cardiomyocytes were measured.The expression of hypertrophy associated protein ANP was detected.Results1 Fuyang Qiangxin Decoction can improve the cardiac function and reduce myocardial hypertrophy in rats with heart failure after myocardial infarctionCompared with model group,EF and FS in low-dose group,high-dose group and positive control group were increased(P<0.001).Compared with model group,LVDd and LVDs in low-dose group,high-dose group and positive control group were decreased gradually(P<0.01).The content of serum NT-proBNP in high dose group was lower than that in model group(P<0.01).The myocardial cells in the infarct margin area were observed by HE staining.The myocardial cells in the model group were arranged sparsely and disordered,and there was inflammatory cell infiltration.The inflammatory infiltration was reduced in the low-dose,high-dose and positive control groups,and the cells in the high-dose and positive control groups were more densely arranged than in the model group.Compared with the blank group and the sham group,the myocardial cells in the other four groups increased significantly.Compared with the model group and the positive control group,the myocardial cells in the low-dose and high-dose groups increased slightly.The βMHC protein content in model group was significantly higher than that in blank group and sham group(P<0.0001).Compared with model group,β-MHC content in lowdose,high-dose and positive control groups was significantly decreased(P<0.01).The content of ANP in model group was significantly higher than that in blank group and sham operation group(P<0.0001).Compared with model group,the content of ANP in low-dose group,high-dose group and positive control group was significantly decreased(P<0.0001).2.Fuyang Qiangxin Decoction may improve mitochondrial energy metabolism by affecting ketone formation and degradationAccording to KEGG enrichment results,differentially expressed mRNAs are mainly enriched in metabolic pathways.Metabolic pathways were selected for further analysis.Through the construction of PPI network,the pathway with the highest enrichment intensity of KEGG pathway was related to ketone body synthesis and degradation.Compared with blank group,serum β-hydroxybutyric acid content in lowdose,high-dose and positive control groups was decreased(P<0.05),but serum βhydroxybutyric acid content in Fuyang Qiangxin decoction group was increased compared with model group.ATP content in myocardial tissue of low-dose and highdose groups was higher than that of model group(P<0.01).The mitochondria of the model group showed swelling,enlarged and rounded mitochondria,shallow matrix,shorter and less crista or even disappeared,and vacuoles.The mitochondrial crista of the low-dose group and positive control group were less or broken,but lighter than that of the model group.The mitochondrial changes of the high-dose group were small,complete in morphology and structure,closely arranged,and no obvious changes in crista.3.Fuyang Qiangxin Decoction can improve the hypertrophy and early apoptosis of H9C2 cardiomyocytesCompared with model group,the cell survival rate of low-dose,medium-dose,high-dose and positive control groups was significantly increased(P<0.0001).The proportion of cells with decreased mitochondrial membrane potential in TCM group was lower than that in AngⅡ group.Compared with model group,ATP content in AngⅡ+2.5mg/ml group,AngⅡ+5mg/ml group and AngⅡ+7.5mg/ml group(P<0.05)after Fuyang Qiangxin decoction intervention gradually increased in a dose-dependent manner.Compared with AngⅡ group,the ANP content in AngⅡ+2.5mg/ml group,AngⅡ+5mg/ml group(P<0.05)and AngⅡ+7.5mg/ml group(P<0.05)was decreased. |
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