Changes Of Iron-related Factors In Acute Ischemic Heart Failure And The Effects Of Luofengning No. 2 Prescription On The

Heart failure is the final clinical stage of the development of various cardiovascular diseases.In recent years,evidence-based medicine has shown that angiotensin receptor/neprilysin inhibitor,sodium glucose cotransporter 2 inhibitors,etc.are the representatives.Newer heart failure drugs have been developed to improve the prognosis of heart failure,however,the prognosis of heart failure patients is still poor.Luo Feng Ning NO.2 prescription is the experience formula of Professor Wang.It was created according to the theory of Endogenous collateral wind proposed by Professor Wang.After years of clinical practice and the polishing of many clinical experts,good results have been achieved.However,the mechanism of Luo Feng Ning NO.2 prescription in the treatment of heart failure is still unclear.Ferroptosis is a newly discovered pathway of cell death that has been implicated in a variety of cardiovascular pathophysiological processes.In this study,animal experiments were used to study the curative effect of Luo Feng Ning NO.2 prescription on acute ischemic heart failure and its effect on the process of ferroptosis in acute ischemic heart failure,and to study the Endogenous collateral wind in heart failure by clinical observation.Changes of TCM syndromes and ferroptosis-related indicators in patients with Endogenous collateral wind and non-Endogenous collateral wind.Objectives:1 To verify the efficacy and safety of Luo Feng Ning NO.2 prescription on the mouse model of acute ischemic heart failure through animal experiments.2 To explore the changes of ferroptosis in the mouse model of acute ischemic heart failure through animal experiments,and to explore the effect of Luo Feng Ning NO.2 prescription on the ferroptosis of the model.3 To explore the change characteristics of TCM syndromes and the changes of ferroptosis-related indicators in patients with acute ischemic heart failure with Endogenous collateral wind and non-Endogenous collateral wind through clinical observation.Methods:Part 1 Experimental ResearchExperiment 1 Effect of Luo Feng Ning NO.2 prescription on cardiac function in mice with acute ischemic heart failureThe C5 7 mouse model of acute ischemic heart failure was established by coronary artery ligation,and randomly divided into sham operation group,operation group,low-dose group of Luo Feng Ning NO.2 prescription,middle-dose group of Luo Feng Ning NO.2 prescription,high-dose group of Luo Feng Ning NO.2 prescription and ACEI group.After two weeks of drug treatment,the weight,food intake,exercise tolerance,left ventricular ejection fraction(LVEF),heart length,weight,cardiac index,hematoxylin-eosin(HE)staining,Masson staining,enzyme-linked immunosorbent assay(ELISA),polymerase chain reaction(PCR),Western blotting(WB),etc.Efficacy in mice with hemorrhagic heart failure.Experiment 2.The effect of Luo Feng Ning NO.2 prescription on ferroptosis pathway in mice with acute ischemic heart failureThe mouse model of acute ischemic heart failure was established by coronary artery ligation,and randomly divided into sham operation group,operation group,Luo Feng Ning NO.2 prescription group,and ferroptosis inhibitor group.Body weight,food intake,LVEF,heart weight,cardiac index,ELISA,PCR,WB,etc.,to explore the changes of ferroptosis in mice with acute ischemic heart failure,and to explore the effect of Luo Feng Ning NO.2 prescription on acute ischemic heart failure.Effects of ferroptosis in mice.Part 2 Clinical ResearchClinical characteristics and changes of ferroptosis-related indicators in patients with acute ischemic heart failure with Endogenous collateral wind and non-Endogenous collateral wind syndrome59 patients with acute ischemic heart failure who met the diagnostic criteria were divided into a Endogenous collateral wind group and a non-Endogenous collateral wind group according to the TCM syndromes at the time of admission.The basic information,past medical history,drug use,coronary arterial lesions,N-terminal precursor B-type natriuretic peptide(NT-proBNP),LVEF,renal function,risk factors for coronary atherosclerotic heart disease,calculate the patient’s TCM syndrome scores,and measure ferroptosis-related indicators by ELISA to explore Changes of TCM syndrome scores and ferroptosis-related indicators in patients with internal movement of collateral wind,and to explore the correlation of related indicators of ferroptosis with acute ischemic heart failure syndrome types and severity of Endogenous collateral wind.Results:Part 1 Experimental ResearchExperiment 1 Effect of Luo Feng Ning NO.2 prescription on cardiac function in mice with acute ischemic heart failure1 Luo Feng Ning NO.2 prescription can improve the symptoms of acute ischemic heart failure in mice:compared with the operation group,there was no statistical difference in body weight,body weight gain,and LVEF among the treatment groups.Higher(P<0.05),higher exercise tolerance(P<0.05).HE staining results showed that the myocardial cells in the middle-dose group of Luo Feng Ning NO.2 prescription were more neatly arranged,smaller in size,and less in the number of inflammatory cells,Masson staining results showed The fibrosis blue staining was less in the middle-dose group of Luo Feng Ning NO.2 prescription.2 Luo Feng Ning NO.2 prescription can reduce the expression of heart failure diagnostic markers and fibrosis and inflammation-related proteins in mice with acute ischemic heart failure:ELISA results showed that compared with the operation group,the low-dose Luo Feng Ning NO.2 prescription level of transforming growth factor β1(TGF-β1)was lower(P<0.05),the level of B-type natriuretic peptide(BNP)in the middle-dose Luo Feng Ning NO.2 prescription group was lower(P<0.05),and the level of TGF-β1 was lower(P<0.01).WB results showed that compared with the operation group,the protein expression levels of Col I and nuclear transcription factor kappa B(NF-κB)in the middle-dose Luo Feng Ning NO.2 prescription group were lower(P<0.05).3 Luo Feng Ning NO.2 prescription can reduce the mRNA expression of heart failure diagnostic markers and fibrosis markers in mice with acute ischemic heart failure:PCR results showed that compared with the operation group,the BNP of the low-dose Luo Feng Ning NO.2 prescription group,collagen type Ⅰ(Col Ⅰ)mRNA expression level was lower(P<0.05),BNP mRNA expression level was lower in Luo Feng Ning NO.2 prescription middle-dose group(P<0.05),Col I mRNA expression level was lower(P<0.01).Experiment 2 The effect of Luo Feng Ning NO.2 prescription on ferroptosis pathway in mice with acute ischemic heart failure1 Luo Feng Ning NO.2 prescription can inhibit the ferroptosis pathway in mice with acute ischemic heart failure:compared with the operation group,there was no statistical difference in body weight,heart weight and cardiac index between the treatment groups.Ultrasound results showed that,compared with the operation group,the left ventricular end-systolic diameters(LVIDs)in the Luo Feng Ning NO.2 prescription group and the ferroptosis inhibitor group were lower than those in the operation group(P<0.01).Mitochondrial cristae were broken,mitochondrial swelling,vacuolization,and disintegration were more serious,showing obvious ferroptosis characteristics.Luo Feng Ning NO.2 prescription and ferrostatin-1 group were different from that.2 Luo Feng Ning NO.2 prescription can inhibit the expression of ferroptosis-related proteins in mice with acute ischemic heart failure:ELISA results showed that compared with the sham operation group,the serum levels of malondialdehyde(MDA)and TGF-β1 in the operation group were higher than those in the sham operation group.Compared with the operation group,the serum MDA level in the Luo Feng Ning NO.2 prescription group was lower(P<0.05),and the level of TGF-βl was lower(P<0.01).WB results showed that compared with the sham operation group,the expression levels of glutathione peroxidase 4(GPX4)and SLC7A11 protein in the operation group were lower(P<0.01),and the protein expression level of ferritin H1(FTH)was lower(P<0.05),compared with the operation group,the expression levels of GPX4 and FTH proteins in the Luo Feng Ning NO.2 prescription group were higher(P<0.05),and the expression levels of GPX4 and FTH in the ferrostatin-1 group were higher(P<0.05).3 Luo Feng Ning NO.2 prescription can inhibit the expression of ferroptosis-related protein mRNA in mice with acute ischemic heart failure:PCR results showed that compared with the sham operation group,the mRNA expression levels of GPX4,FTH1 and SLC7A11 in the operation group were lower(P<0.01).Compared with the operation group,the Luo Feng Ning NO.2 prescription group had higher levels of GPX4 mRNA expression(P<0.05)and higher FTH1 mRNA expression levels(P<0.01);the ferrostatin-1 group had higher levels of GPX4 and SLC7A11 mRNA expression(P<0.05),and the expression level of FTH1 mRNA was higher(P<0.01).Part 2 Clinical ResearchClinical characteristics and changes of ferroptosis-related indicators in patients with acute ischemic heart failure with Endogenous collateral wind and non-Endogenous collateral wind syndrome1 Compared with non-Endogenous collateral wind group patients,there were no differences in age,gender,medical history,Killip grade,coronary angiography coronary artery disease,and medication use during hospitalization in Endogenous collateral wind group patients..2 Compared with the patients with non-Endogenous collateral wind group,the patients in the Endogenous collateral wind group were induced or aggravated by emotional changes in the single item of wind pathogenic syndrome,increased wind speed and other weather mutations,chest pain≥2 places,fear of wind The incidence was higher(P<0.01).3 The ELISA results showed that compared with the non-Endogenous collateral wind patients,the ferroptosis-related serological indexes GPX4 and FTH1 levels were lower(P<0.01),and the MDA level was higher(P<0.05).4 Compared with patients with non-Endogenous collateral wind,there was no difference in MACE events during hospitalization in the Endogenous collateral wind group,and the NT-proBNP was higher before discharge in the Endogenous collateral wind group(P<0.05).Conclusions:1 Luo Feng Ning NO.2 prescription is safe and effective for the C57 mouse model of acute ischemic heart failure,and can significantly improve the quality of life,exercise tolerance and heart failure-related indicators of mice.2 The ferroptosis pathway is activated in the animal model of acute ischemic heart failure.The therapeutic effect of Luo Feng Ning NO.2 prescription on the animal model of acute ischemic heart failure is related to the inhibition of the ferroptosis pathway.3 Acute ischemic heart failure patients with Endogenous collateral wind have severe symptoms,high TCM syndrome scores,and poor prognosis.Activation of the ferroptosis pathway may be the underlying reason for the severe disease in these patients.