| Objective:A randomized controlled trial was conducted to observe the clinical efficacy and safety of Shuxin decoction in patients with Heart failure with preserved ejection fraction(HFp EF)syndrome of Qi deficiency and blood stasis.To analyze the targets and signaling pathways of Shuxin decoction in the treatment of HFp EF,and explore its possible mechanism of action.Methods:1.Sixty inpatients and outpatients in the Department of Cardiology,First Affiliated Hospital of Anhui University of Traditional Chinese Medicine were selected and randomly divided into a control group and an observation group,with 30 patients in each group.The control group was treated with routine western medicine,while the observation group was treated with Shuxin decoction for 4 weeks on the basis of the control group,and the patients with HFp EF of qi deficiency and blood stasis were evaluated comprehensively respectively.The changes of curative effects indicators such as TCM syndrome efficacy,TCM syndrome score,cardiac function,quality of life,N-terminal B-type natriuretic peptide precursor,and echocardiography(E/A,E/E’)and safety indicators before and after treatment were compared between the two groups.2.The database platform was used to search the chemical components in Shuxin Decoction and their action targets in human body,to explore the potential targets of the disease named "heart failure with preserved ejection fraction",to construct a "compound-action target" network,and to obtain the key targets of the active components for enrichment analysis.Results:1.Clinical study results:(1)TCM syndrome curative effect: the total effective rate of the observation group was 86.67%,while that of the control group was 70.0%,and the total effective rate of the observation group was more significant(P < 0.05).TCM syndrome scores showed that the scores of the two groups decreased after treatment(P < 0.05),and the score in the observation group was better than that in the control group(P < 0.05).(2)Cardiac function:(1)NYHA cardiac function classification: the total effective rate was 90.0% in the observation group and 73.3% in the control group,and the improvement in the observation group was more significant(P < 0.05).(2)6-minute walk test: the walking distance of the two groups increased after treatment,and the distance of the observation group increased more significantly(P < 0.05).(3)The quality of life score of heart failure: the quality of life score was lower than before(P < 0.05),and the curative effect of the observation group was better(P < 0.05).(4)N-terminal pro-B-type natriuretic peptide and echocardiography(E/A,E/E’):After treatment,N-terminal pro-B-type natriuretic peptide decreased(P < 0.05),E/A increased(P < 0.05),and E/E’ decreased(P < 0.05)in the two groups.The observation group was better than the control group(P < 0.05).The safety indicators of the two groups were not significantly abnormal before and after treatment.2.Experimental results of network pharmacology:(1)There were 96 active components and 1534 target proteins in Shuxin decoction.There were 341 nodes and 1388 links in the target network,and the top four ranked by degree value were quercetin,kaempferol,luteolin and tanshinone IIA.(2)239 HFp EF disease genes were obtained in this study.(3)The PPI network of Shuxin decoction for HFp EF was constructed in this study,including 21 nodes and 127 connections.The top 10 network nodes with connectivity values were TNF,IL-1β,MMP9,EDN1,SERPINE1,MMP2,NOS3,CAV1,CRP,and HIF1 A.(4)Functional enrichment analysis: most of the biological processes of HFp EF treatment were enriched in the response of cells to lipids,regulation of apoptosis signaling pathway,negative regulation of apoptosis signaling pathway,response to lipopolysaccharide,and regulation of angiogenesis.KEGG analysis showed that the treatment of HFp EF was mainly related to the fluid shear stress and atherosclerosis pathway,relaxin signaling pathway,HIF-1 signaling pathway,and Apelin signaling pathway.Conclusions:1.This study found that Shuxin decoction combined with conventional western medicine in the treatment of HFp EF patients with qi deficiency and blood stasis syndrome has better efficacy than simple western medicine in alleviating symptoms of heart failure,improving cardiac function,improving quality of life,reducing the level of N-terminal pro-B-type natriuretic peptide,and improving echocardiographic indicators.2.Through network pharmacology analysis,it is found that this recipe contains a large number of active ingredients such as quercetin,kaempferol,luteolin,tanshinone IIA,etc.It may play a regulatory role in regulating lipid metabolism,responding to hypoxia,regulating angiogenesis,immune response,and regulating apoptosis by affecting TNF,IL-1β,MMP9,EDN1,SERPINE1,MMP2,NOS3,CAV1,CRP,HIF1 A and other core targets to alleviate the occurrence and development of HFp EF. |