Effect Evaluation And Mechanism Study Of Baoyuan Decoction And Xuefuzhuyu Decoction In Treating Heart Failure With Preserved Ejection Fraction(Qi Deficiency And Blood Stasis Type)in The Elderly

Objective: To observe the clinical efficacy and prognosis of Bao Yuan Tang combined with Blood Mansions and Blood Stasis Tang on elderly patients with Qi deficiency and blood stasis type of heart failure with preserved ejection fraction(HFp EF),and to explore its target pathways and mechanism of action using a network pharmacology approach.Methods:(1)This study was a non-blinded randomized controlled study that included 114 elderly patients with NYHA cardiac function class II-III HFp EF who were admitted to the 960 th Hospital of the People’s Liberation Army from October 1,2021 to November 30,2022,and were randomly divided into the Chinese medicine group(n=57)and the control group(n=57).The control group patients were given a conventional treatment plan,while the traditional Chinese medicine group patients were treated with Baoyuan Tang and Xuefu Zhuyu Tang in addition to the control group,with a treatment course of 1 month.The time when the observation subjects were enrolled in this study was used as the starting point for follow-up,and the time of all-cause death or the end of follow-up(November 30,2022)was used as the follow-up endpoint.The primary endpoint event was the patient’s acute heart failure episode during the follow-up period,and the secondary endpoints were the TCM evidence score,heart failure score,quality of life assessment and biochemical indicators of cardiac function and safety assessment(before,1 month and 3 months after treatment).(2)Using a web-based pharmacology approach,the active ingredients and targets of Po-Yuan Tang combined with Blood Mansions and Blood Stasis were searched using the TCMSP and TCMID online databases,and the disease targets associated with HFp EF were obtained from Gene Cards,OMIM,TTD,Drug Bank and Dis Ge NET data platforms,using Cytoscape 3.7.2 software to The drug-disease targets were intersected and analysed using Cytoscape 3.7.2software to obtain core protein interaction(PPI)networks,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed to create bar and bubble plots.Results:(1)Comparison of baseline data such as age,gender,history of smoking and alcohol consumption,cardiovascular disease duration,comorbid diseases and medication use between the two groups showed no statistically significant differences;(2)Comparison of the primary endpoint: the risk of acute heart failure attack during the follow-up period was reduced by 47.6%in patients after the combined use of Chinese medicine compared with conventional treatment;(3)Comparison of secondary endpoints: After one month of treatment,the total effective rate of NYHA heart function grading,heart failure score,traditional Chinese medicine syndrome score,and quality of life score of the two groups were better in the traditional Chinese medicine group than in the control group(P<0.05),with NT pro BNP and h FABP levels lower than in the control group(P<0.05),and LVEF values higher than in the control group(P<0.05);The follow-up results in the third month showed that there was no statistically significant difference in the total effective rate of heart function and heart failure score,NT-pro BNP,h FABP between the traditional Chinese medicine group and the control group.(4)Safety comparison: the differences in laboratory results between the two groups were not statistically significant when compared between groups at month 1 of treatment and month 3 of follow-up;(5)A total of 147 drug-disease intersection targets were screened by network pharmacology analysis,including JUN,HIF1 A,TP53,ESR1,MYC,MAPK1,MAPK14,AKT1(6)GO analysis revealed that the active ingredients and targets were mainly involved in biological processes such as response to hypoxia,negative and positive regulation of apoptosis,ageing and positive regulation of cell proliferation,suggesting that the therapeutic effect of Baoyuan Tang combined with Xuifu Bangyu Tang on HFp EF patients is mainly in the inhibition of apoptosis.(7)KEGG analysis revealed that the target genes were mainly enriched in 174 signaling pathways,including lipid and atherosclerosis,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,and fluid shear stress and atherosclerosis,suggesting that Bao Yuan Tang combined with Blood Fu Yi Yu Tang may have a beneficial effect on HFp EF patients by modulating the apoptosis process,alleviating the hypoxic stress response and delaying myocardial aging.This suggests that the combination of Blood Mansions and Blood Stasis Tang may be involved in the treatment of HFp EF by modulating the above pathways.Conclusion: The combination of Bao Yuan Tang and Blood Mansions and Evacuating Blood Stasis Tang can reduce the blood NT-pro BNP and h FABP levels of patients,improve the clinical symptoms,improve the TCM evidence score,improve the quality of life,maintain the stability of left ventricular ejection fraction and reduce the risk of acute heart failure attacks in patients with HFp EF.According to the pharmacological analysis of the network,the mechanism of action of the combination of Bao Yuan Tang and Xifu Ban Yu Tang may be related to the regulation of JUN,HIF1 A,TP53,ESR1,MYC,MAPK1 and other targets,intervention of lipid and atherosclerosis,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications and other pathways,which can improve the physiological status of myocardium,to a certain extent,and It can improve myocardial physiological status,reduce apoptosis,and exert anti-inflammatory responses,improve myocardial microcirculation,and regulate blood glucose and lipid levels,thus achieving the effect of delaying the progression of heart failure.