| Objective:1 To observe the clinical efficacy of Yiqi Wenyang Huoxue Lishui Formula in treating acute heart failure with preserved ejection fraction.2 To explore the network pharmacological mechanism of Yiqi Wenyang Huoxue Lishui Formula in treating acute heart failure with preserved ejection fraction.Methods:1 Using a randomized controlled study method,a total of 60 patients with acute heart failure with preserved ejection fraction(AHFpEF)who met the inclusion criteria were randomly divided into an observation group and a control group of 30 cases each.The control group received conventional Western medicine treatment and placebo,while the observation group received Yiqi Huoxue Wenyang Lishui Formula on top of conventional Western medicine treatment for 7 days.Record the baseline data of the patients before and after treatment,observe the NYHA cardiac function grading and efficacy,traditional Chinese medicine syndrome score and efficacy,NT proBNP level,changes in myocardial injury markers(including cTnI,CKMB,Myo),and changes in liver and kidney function indicators(including ALT,AST,CREA)of the two groups of patients before and after treatment,and follow up the 28 day survival status of the patients after enrollment by phone to compare the 28 day survival rate of the two groups of patients.2 The active ingredients and targets of Yiqi Wenyang Huoxue Lishui Recipe were screened through the Systems pharmacology database and analysis platform of traditional Chinese medicine(TCMSP),and the "traditional Chinese medicine active ingredients target" network was constructed and analyzed with Cytoscape 3.9.1;Retrieve and screen the targets of AHFpEF from Genecards and OMIM databases,and select the intersection targets of Yiqi Wenyang Huoxue Lishui Formula and AHFpEF through the venny online platform;Import intersection targets into the STRING database to construct protein interaction(PPI)networks;Construct an active ingredient intersection target network using Cytoscape 3.9.1;Use R language to conduct GO functional enrichment analysis and KEGG pathway enrichment analysis on intersection targets,and explore the network pharmacological mechanism of Yiqi Wenyang Huoxue Lishui Formula in treating AHFpEF.Results:1 Clinical observation results:A total of 60 patients were included in the clinical study.There was no statistically significant difference in baseline data between the two groups of patients at the time of enrollment,indicating comparability(P>0.05).1.1 There was a significant difference in NYHA cardiac function grading between the two groups of patients before and after treatment within the group(Pintra<0.05),while there was no statistically significant difference between the groups(Pinter>0.05).The total effective rates of the observation group and the control group were 76.7%and 56.7%,respectively.There was no statistically significant difference in the improvement effect of NYHA cardiac function grading(P>0.05).1.2 After treatment,there was a significant difference in the TCM syndrome score between the two groups(t=2.800,P=0.007).After treatment,the TCM syndrome score of the observation group decreased by 15.50 points(95%CI:12.80-16.94)compared to before,while the TCM syndrome score of the control group decreased by 12.00 points(95%CI:10.07-12.15).The TCM syndrome score of the observation group decreased better than that of the control group,with a difference of about 3.50 points(Z=-2.123,P=0.034).The total effective rates of the observation group and the control group were 90.0%and 70.0%,respectively.The therapeutic effect of improving traditional Chinese medicine syndrome scores in the observation group was better than that in the control group(Z=-2.230,P=0.044).1.3 There was a significant difference in NT-proBNP between the two groups after treatment(Z=-2.159,P inter=0.031).There was a significant decrease in NT-proBNP in both groups after treatment compared to before(Z=-4.556 in the control group and Z=-4.741 in the observation group,P intra<0.001);NT-proBNP decreased by 3247.50 pg/ml after treatment in the observation group compared to before,and NT-proBNP decreased by 1758.00 pg/ml after treatment in the control group.The difference between before and after NT-proBNP in the observation group was better than that in the control group(Z=-2.144,P=0.032).1.4 In the observation group,there was a significant decrease in cTnI and Myo after treatment compared to before treatment(cTnI:Z=-2.224,Pin group=0.026;Myo:Z=-2.983,Pintra=0.003),while there was no statistical difference in CK-MB before and after treatment(Pintra>0.05);in the control group,there was no statistically significant difference in all three indicators of the control group before and after treatment(Pintra>0.05).1.5 There was no statistically significant difference in ALT,AST,and CREA between and within the two groups before and after treatment(P>0.05),indicating good safety.1.6 Both the control group and the observation group had 27 survival cases,3 deaths,and a 28 day survival rate of 90.0%,with no statistical difference(P>0.05).Kaplan Meier survival analysis showed no statistically significant difference in 28 days survival status between the two groups(Log Rank P=1.000).2 Research results of network pharmacology:129 active ingredients and 261 action targets of Yiqi Wenyang Huoxue Lishui Formula were obtained from the TCMSP database.1465 AHFpEF disease targets were retrieved from the gene database,and 126 intersection targets of traditional Chinese medicine prescriptions and diseases were obtained.The key active ingredients in traditional Chinese medicine formulas are quercetin,kaempferol Glutosterol,luteolin,isorhamnetin,7-O-methyl-isopiconosyl,tanshinone ⅡA,formononetin,and the key targets are MAPK1,TP53,STAT3,AKT-1,RELA,TNF,MAPK14,ESR1,IL-6,CTNNB1.GO function enrichment analysis and KEGG pathway enrichment analysis obtained 2800 function enrichment items and 167 signal pathways respectively,mainly involving biological processes such as response to reactive oxygen species,oxidative stress,response to lipopolysaccharide,cytokine receptor binding,as well as AGE-RAGE,lipid and atherosclerosis,blood flow shear and atherosclerosis,TNF,HIF-1,IL-17,PI3K Akt and other signal pathways.Conclusions:1 On the basis of conventional Western medicine treatment,combined with the Yiqi Wenyang Huoxue Lishui Formula,there is no significant difference in improving NYHA heart function grading,reducing heart damage indicators(cTnI,CK-MB,Myo),and increasing 28 day survival rate.However,it can effectively improve the clinical symptoms of AHFpEF patients,reduce NT proBNP levels,and have no significant impact on liver and kidney function,with good safety.2 The ingredients in the Yiqi Wenyang Huoxue Lishui Formula are rich and can treat AHFpEF through multiple targets,biological processes,and pathways.Quercetin,kaempferolβ-The active ingredients,such as sitosterol,luteolin,isorhamnetin,7-O-methyl-isopiconosyl,tanshinone IIA,formononetin,regulate AGE-RAGE,lipid and atherosclerosis,blood flow shear and atherosclerosis,TNF,HIF-1,IL-17,PI3K-Akt and other signal pathways through MAPK1,TP53,STAT3,AKT-1,RELA,TNF,MAPK14,ESR1,IL-6,CTNNB1 and other targets to play a therapeutic role in AHFpEF. |
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