Retrospective Study And Metabolomics Analysis Of Xueshuantong Injection In The Adjuvant Treatment Of Myocardial Infarctio

Objective:A randomized controlled clinical trial had demonstrated the efficacy of thrombus injection in the adjuvant treatment of myocardium infarction(MI).However,in the real world,the efficacy of thrombus injection in the treatment of myocardial infarction remains unclear.Based on clinical retrospective study,this study evaluated the efficacy of Xueshuantong for injection in the adjuvant treatment of MI,and explored its effective mechanism.Study 1:Methods:In this study,clinical data of 456 patients with MI admitted to the second ward of the Department of Cardiovascular Disease(including CCU 2 Ward)of Dongzhimen Hospital from January 1,2017 to December 31,2021 were retrospectively collected based on diagnostic criteria and exclusion criteria.Among them,256 MI patients who received both conventional treatment and Xueshuantong for injection were included in the Xueshuantong group.208 MI patients received conventional treatment only and were included in the non-xueshuantong group.The primary outcome was the 28-day incidence of major adverse cardiovascular events(MACE)in MI patients.MACE include cardiogenic death,cardiogenic shock,heart failure,recurrent severe angina pectoris,recurrent MI,target vessel revascularization,and severe arrhythmia.Secondary outcome measures were 28-day mortality in MI patients,7-day left ventricular ejection fraction,peak troponin and time required to return to normal levels during hospitalization,length of hospitalization,and rate of re-admission to the cardiovascular department of our hospital for cardiogenic factors within 1 year.Results:Main outcome indicators:The 28-day incidence of MACE in MI patients undergoing percutaneous coronary intervention(PCI)in the Xueshuantong group was 4.67%,and that in MI patients undergoing PCI in the non-Xueshuantong group was 14.93%,with statistical significance(P<0.001).Secondary outcome indicators:The 28-day mortality rate of MI patients in the Xueshuantong group after PCI was 0.93%,and that in the nonXueshuantong group was 5.22%,with statistical significance(P<0.05).There were no significant differences in 7-day left ventricular ejection fraction,the peak of troponin during hospitalization and the time required to recover to normal level,the length of hospitalization and the rate of re-admission to the cardiovascular department of our hospital within 1 year due to cardiogenic factors(P>0.05).Conclusion:The use of Xueshuantong for injection during hospitalization reduced the 28-day incidence of MACE and 28-day mortality in MI patients undergoing PCI.Study 2:Methods:Twelve patients with acute ST-segment elevation MI who met the diagnostic criteria and exclusion criteria were randomly divided into Xueshuantong group and nonXueshuantong group with 6 cases in each group by random number table method from October 1,2020 to December 31,2020 in the second ward of the Cardiovascular Department of Dongzhimen Hospital of Beijing University of Chinese Medicine.Based on the conventional treatment of MI patients in the non-Xueshuantong group,150mg of Xueshuantong for injection was given intravenously immediately after admission,300mg of intravenous infusion after PCI,and 450mg of intravenous infusion was given daily for 6 days.Blood samples were collected from both groups on day 7 of admission and nontargeted metabolomics analysis was performed using UHPLC-tandem Fourier transform mass spectrometry(UHPLC-QExactive).Results:A total of 601 metabolites were found in this study,including 594 metabolites in the Xueshuantong group,570 metabolites in the non-Xueshuantong group,563 metabolites in common between the two groups,and 71 different metabolites meeting the screening criteria.Among them,52 differential metabolites were up-regulated and 19 were down-regulated.Among the up-regulated differential metabolites,significant differences were trehalose,panax notoginseng saponin Fa,ginsenoside Rh3,ginsenoside Rb1,panax notoginseng saponin A,ptaeroxylin,ginsenoside Rg5,betulin,a-curcumene,ginsenoside Re,etc.Among the down-regulated differential metabolites,the significant differences were 4acetylaminobutyrate,trigonellamide,trimethylpyridine,guava acid,etc.The network pharmacological analysis of the metabolites of Xueshuantong showed that VEGFA,AKTI and other proteins may be the key proteins in the adjuvant therapy of Xueshuantong MI.Positive cell migration regulation pathway,proteolytic pathway,inflammatory response pathway,extracellular region pathway,cell membrane pathway,extracellular space pathway,serine endopeptidyase activity pathway,serine/threonine/tyrosine kinase activity pathway,identical protein binding pathway,Kaposi sarcoma-associated herpes virus infection pathway,AGE-RAGE signaling in diabetic complications Pathway and epidermal growth factor tyrosine kinase inhibitor resistance pathway may be an important pathway for Xueshuantong adjuvant treatment of MI.Conclusion:The content of trehalose,4-acetylaminobutyrate and other substances in MI patients was significantly regulated by Xueshuantong.Its clinical efficacy is closely related to VEGFA,AKTI and other proteins,as well as the positive regulation pathway of cell migration and proteolytic pathway.