The Relationship Between SIRT3 Expression And Oxidative Stress In Patients With Chronic Heart Failure

Background:Chronic heart failure(CHF)is a group of syndromes in which various cardiac structures or functional diseases cause the heart's systolic and dysfunctional function to cause absolute or relative decrease in cardiac output,which cannot meet the metabolic needs of the body.Despite the great development of medical technology,the efficacy of heart failure has been improved.However,as the final stage of the development of most cardiovascular diseases,heart disease is the only one with the current prevalence,morbidity and mortality.Increased cardiovascular disease.Therefore,in-depth exploration of the pathogenesis of heart failure can provide ideas and basis for clinical treatment.At present,understanding heart failure is a disease that is constantly evolving.When the heart load is overweight and the myocardial systolic function is impaired,it can activate a variety of complex interaction compensation mechanisms,in which cardiac remodeling and oxidative stress are involved.It plays an important role in the development of heart failure.SIRT3(Sirtuins3)is an important mitochondrial NAD+-dependent deacetylase.In recent years,the research of SIRT3 gene in the field of cardiovascular disease has attracted the attention of scholars.SIRT3 not only expresses at a high level in the mitochondria,but also increases its expression level in the nucleus of cardiomyocytes.It has anti-apoptotic effect on protecting cardiomyocytes and inhibiting the occurrence of cardiac hypertrophy.At the same time,SIRT3 plays an important role in the process of scavenging reactive oxygen species(ROS).Therefore,SIRT3 may protect the heart by inhibiting the oxidative stress injury response in heart failure.This clinical study aimed to investigate the expression changes of SIRT3 in patients with chronic heart failure and its relationship with oxidative stress levels and cardiac remodeling.Objectives1.To compare the expression levels of SIRT3 mRNA in HFpEF group,HFmrEF group,HFrEF group and control group by measuring the expression level of SIRT3 mRNA in peripheral blood mononuclear cells(PBMCs)of patients with CHF,and to explore the role of SIRT3 in the development of CHF.2.The relationship between the levels of SOD,MAD,and 8-OHdg in patients with CHF was compared in each group to investigate the relationship between oxidative stress and heart failure in CHF patients.3.To investigate the possible role of SIRT3 in oxidative stress injury of heart failure by comparing oxidative stress level and SIRT3mRNA gene level in CHF patients.4.To compare the relationship between SIRT3 and cardiac remodeling by comparing SIRT3mRNA gene expression level and cardiac remodeling index in each group.Method:Among patients who were admitted to the Department of Cardiology of the Second Hospital of Shandong University from September 2017 to September 2018,patients with heart failure who met the diagnostic criteria in the "2018 Guidelines for the Diagnosis and Treatment of Heart Failure in China" were selected and followed by the left ventricle of the patient.The ejection fraction was divided into heart failure patients with reduced ejection fraction(HFrEF group,20 patients),heart failure group with middle-range ejection fraction(HFmrEF group,20 patients),and heart failure score-retained heart failure group.(HFpEF group,20 cases).Twenty patients with normal cardiac function in the same period were used as the control group.To assess the differences between the control group and the subgroups of heart failure,patients were carefully asked about their medical history(including age,smoking history,history of hypertension,history of diabetes,etc.),and blood uric acid,total cholesterol,and low-density lipoprotein were measured.Biochemical indicators such as cholesterol,high-density lipoprotein,and fasting blood glucose.The relative expression levels of SIRT3 mRNA in peripheral blood mononuclear cells(PBMCs)of all selected subjects were detected by RT-PCR.The concentrations of SOD,MDA and8-OHdG in the serum of the selected subjects were detected by ELISA.Echocardiography was used to measure LAD,LVEDd,LVEDV,LVEF and other indicators in each group to investigate the role of SIRT3 in the development of heart failure and its relationship with oxidative stress and cardiac remodeling.Result:1.There were significant differences in SIRT3mRNA expression levels between the groups(F=14.292,P<0.01).The expression of SIRT3mRNA in the control group was 1.25 times higher than that of HFpEF(P<0.05).The expression of SIRT3mRNA in the control group was 1.64 times higher than that in the HFmrEF group(P<0.01),and the expression of SIRT3mRNA in the control group was 3.2 times higher than that in the HFrEF group(P<0.01).The levels of SIRT3mRNA in HFpEF group was significantly higher than that in HFmrEF group and HFrEF group(P<0.01).The levels of SIRT3mRNA in HFmrEF group was significantly higher than that in HFrEF group(P<0.01).2.The serum MDA level was significantly lower in the control group than in the HFpEF group,HFmrEF group and HFrEF group,and the difference between the groups was statistically significant(P<0.01).The level of serum SOD was higher in the control group than in the HFrEF group.HFmrEF and HFpEF groups,and the differences between the groups were statistically significant(P<0.01).The serum 8-OHdG concentration in the control group was(5.25±1.62)ng/ml,the serum 8-OHdG concentration in the HFpEF group was(9.81±1.79)ng/ml,and the serum 8-OHdG concentration in the HFmrEF group was(12.66±1.45)ng/ml.Serum serum 8-OHdG concentration(14.0912.31)ng/ml,in HFrEF group,serum 8-OHdG concentration was significantly lower in the control group than in the heart failure subgroup,and the differences between the groups were statistically significant.Significance(P<0.01).3.Through Pearson correlation analysis,SIRT3mRNA expression was positively correlated with SOD,the correlation coefficient r was 0.505(P<0.01),and negatively correlated with MDA and 8-OHdG.The correlation coefficients r were-0.411 and-0.433(P<0.01).4.Through Pearson correlation analysis,SIRT3mRNA expression was positively correlated with LVEF,and the correlation coefficient r was 0.587(P<0.01),which was negatively correlated with LVEDd,LVEDV and LAD.The correlation coefficients r were-0.265,-0.489,-0.626(P<0.05).conclusion:1.In patients with chronic heart failure,there are changes in SIRT3 gene expression,oxidative stress and imbalance of antioxidant stress,and cardiac remodeling.These changes are aggravated with the decrease of SIRT3 gene expression,suggesting that SIRT3 is in patients with heart failure.The heart protects the heart.2.Left ventricular ejection fraction was negatively correlated with 8-OHdG and MDA levels,and positively correlated with SOD level,indicating that with the decrease of left ventricular ejection fraction in patients with heart failure,serum 8-OHdG,MDA levels increased,SOD levels decreased.It indicates that with the decrease of left ventricular ejection fraction,the presence of antioxidant substances,increased oxidative toxicity products and increased oxidative stress levels suggest that oxidative stress may be involved in the occurrence and development of heart failure.3.The decrease of SIRT3 gene expression and the increase of oxidative stress in patients with chronic heart failure are related to cardiac remodeling in heart failure,suggesting that SIRT3 gene is a protective factor in patients with heart failure,and SIRT3 may affect the body's oxidation.The agonistic reaction is involved in the cardiac remodeling process.