| Objective:Based on network pharmacology technology,the active ingredients,targets,and signaling pathways of Jiawei Danshen Decoction(JWDS)for the prevention of myocardial ischemia-reperfusion injury(MIRI)were predicted,and the compound pretreatment experiment was studied by meta-analysis technology,and finally,the experimental study was verified.Methods:1.The active ingredients and targets related to the pharmacological effects of JWDS were obtained through the TCMSP,UniProt database,and SwissTarget Prediction database,and further searched for literature supplementation.Access to MIRI-related targets through the GeneCards,OMIM,and DRUGBANK databases;String is used to analyzing protein interactions,build PPI networks,and explore potential protein functional blocks.Metascape was used to analyze the biological processes and signaling pathways associated with "drug-ingredient-target",and the next step was to use Cytoscape 3.7.1 to map the "JWDS ingredient-disease target-pathway" network.2.The effect of different compound pretreatment times on myocardial infarction areas in animal MIRI models was studied by meta-analysis techniques.CNKI,WANFANG DATA,Sino Med,PubMed,Web of Science,Cochrane library,and other databases were comprehensively searched,and related journals were also included in the manual search.The quality of the literature was assessed using the Cochrane Reviewer’s Manual 5.1.0 and finally the Review Manager 5.3 analysis.3.After 1 week of pretreatment with JWDS,the experimental rat MIRI model was established by ligation.Experimental observations were performed by enzyme-linked immunosorbent assay(ELISA),real-time PCR(qRT-PCR),western blot,and histopathological staining.Results:1.The results of network pharmacology data analysis showed that 102 active ingredients,140 disease and drug cross-genes,and 54 core targets were obtained after the screening.Targets such as Akt1,JUN,STAT3,and PTGS2 may be closely related to the prevention of MIRI by JWDS,and the KEGG enrichment results predict that 20 pathways,including the Pathways in cancer pathway,are associated with the prevention of MIRI by JWDS,and both Aktl and PTGS2 exist in five of these major pathways.2.The results of the meta-analysis showed that MD=-12.43%with a 95 confidence interv al[-16.25,-8.61]in the short-term pretreatment group and MD=-14.96%in the long-term pretreatment group with a 95 confidence interval[-17.83,-12.08].Sensitivity analysis and subgroup analysis showed that experimental variables had no significant effect on observed infarct limitation.3.The results of animal experiments showed that JWDS could significantly increase the levels of serum malondialdehyde(MDA),creatine kinase isoenzyme MB(CK-MB),lactate dehydrogenase(LDH)(P<0.05)in MIRI rats,reduce the level of superoxide dismutase(SOD)(P<0.05),inhibit the expression levels of Aktl and PTGS2(P<0.05)in myocardial tissue,and reduce myocardial tissue necrosis.Conclusion:1.Network pharmacology predicted that targets such as PTGS2 and Aktl may be important targets for the prevention of MIRI by JWDS,and Akt1 and PTGS2 existed simultaneously in five pathways,including Pathways in cancer.2.The effect of reducing infarct area was not significantly different between 5 and 15 days of TCM compound pretreatment,and the effect of reducing infarct area was independent of animal sex and strain,and the results suggested that there was still room for shortening the pretreatment time of TCM compound.3.Drinking with JWDS may inhibit the two targets of Aktl and PTGS2 at the same time,thereby preventing excessive myocardial damage and preventing MIRI. |
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