Study On The Mechanism Of The Anti-myocardial Ischemia Reperfusion Injury Of Tanyu Tongzhi Recipe Based On Optimized Algorithm

ObjectiveMyocardial ischemia-reperfusion injury(MI/RI)often occurs in heart surgery,coronary artery bypass grafting,recanalization after myocardial infarction,heart transplantation and shock.It has become a common and serious complication after revascularization complication.After years of clinical observations,the research team has found the anti-MI/RI efficacy of it.Self-developed prescription Tan-Yu Tongzhi Prescription is significant.Therefore,this study intends to adopt network pharmacology research methods and apply optimized new algorithms to construct the anti-MI/RI network.The network explores the core pharmacodynamic material basis,potential targets and molecular network mechanism of anti-MI/RI of Tan-Yu Tongzhi Prescription,and provides a reference for the application of the optimized new algorithm to network pharmacology research in the field of Chinese medicine.Methods1.Research on the molecular network mechanism of anti-MI/RI of Tan-Yu Tongzhi Prescription based on the optimized algorithmUse OMIM database,GeneCards database,DisGeNET database and Pubmed database to obtain MI/RI targets.Use TCMSP database,TCMID database and chemical professional database to obtain components.Use SwissADME database to screen active components and use SwissTargetPrediction database to predict the target of active components.Mapping the target of the active ingredients of the traditional Chinese medicine of Tan-Yu Tongzhi Prescription and the target of MI/RI,the potential targets of the anti-MI/RI of Tan-Yu Tongzhi Prescription were obtained,and the core potential targets were screened out using the String database.Use cytoscape 3.7.2 software to construct a network diagram of the relationship between "active ingredients of traditional Chinese medicine-targets-MI/RI" of Tan-Yu Tongzhi Prescription,calculate the network efficacy value of anti-MI/RI of active ingredients of traditional Chinese medicine of Tan-Yu Tongzhi Prescription,and obtain Tan-Yu Tongzhi Prescription Anti-MI/RI core Chinese medicine active ingredient.The Cluego plug-in was used to enrich and analyze the core targets of Tan-Yu Tongzhi Prescription against MI/RI,and to explore the possible potential mechanism of anti-MI/RI of Tan-Yu Tongzhi Prescription.In order to discover its possible potential mechanism more accurately,this study optimized the random walk algorithm,formed a biased restart random walk algorithm based on the average shortest path,and verified the algorithm.The optimized algorithm is applied to construct the networkdiagram of the "active ingredients-target-MI/RI" of Tan-Yu Tongzhi Prescription to obtain the possible potential core targets of the Tan-Yu Tongzhi Prescription against MI/RI,and to apply Cluego The plug-in conducts enrichment analysis on core targets,and explores the possible potential mechanism of anti-MI/RI of Tan-Yu Tongzhi Prescription.2.Study on the molecular network mechanism of anti-MI/RI of the phlegm-removing traditional Chinese medicine group/the traditional Chinese medicine group of the blood stasis-removal of Tan-Yu Tongzhi PrescriptionThe TCMSP database,TCMID database and chemistry database are used to obtain the traditional Chinese medicine components of the phlegm-removing Chinese medicine group/blood stasis-removing Chinese medicine group.The SwissADME database is used to screen out the active ingredients of Chinese medicine,and the SwissTargetPrediction database is used to predict the target of the active ingredient of Chinese medicine.Mapping the target of the active ingredient of the traditional Chinese medicine in the phlegm-removing Chinese medicine group of the Tan-Yu Tongzhi Prescription/the target of the active ingredient of the traditional Chinese medicine in the blood stasis-removing group and the target of MI/RI respectively,the Tan-Yu Tongzhi Prescription phlegm-removing Chinese medicine group/the traditional Chinese medicine group for blood stasis-removing anti-MI/RI potential possible targets of MI/RI.Use the String database to obtain the core targets of the phlegm-removing Chinese medicine group/blood stasis-removing Chinese medicine group.Use the DAVID database to enrich and analyze the anti-MI/RI core targets of the phlegm-removing Chinese medicine group/blood stasis-removing Chinese medicine group and explore the possible potential mechanism of anti-MI/RI of the phlegm-removing Chinese medicine group/blood stasis-removing Chinese medicine group.Results1.Research on the molecular network mechanism of anti-MI/RI of Tan-Yu Tongzhi Prescription based on the optimized algorithm(1)A total of 1283 MI/RI targets;(2)a total of 683 active ingredients in the traditional Chinese medicine of Tan-Yu Tongzhi Prescription,and a total of 1452 predicted targets;(3)a total of 398 anti-MI/RI targets of Tan-Yu Tongzhi Prescription and a total of 337 core targets were obtained using the String database;(4)a network diagram of the“active components of traditional Chinese medicine-targets-MI/RI"of the Tan-Yu Tongzhi Prescription built using the cytoscape 3.7.2 software,with a total of 885 nodes and 12462 items.At the same time,according to the calculated network efficacy value,the core Chinese medicine active ingredients of Tan-Yu Tongzhi Prescription against MI/RI were obtained;(5)the enrichment analysis of 337 core targets of Tan-Yu Tongzhi Prescription against MI/RI showed that:a total of 986 biological reaction processes by GO analysis and a total of 79 KEGG signal pathways;(6)based on the optimized average shortest path bias restart random walk algorithm to construct a core network of“active components of Tanyu Tongzhi prescription-targets-MI/RI",there are a total of 269 nodes,32 nodes for active ingredients of traditional Chinese medicine and 237 disease target nodes.The molecular docking method and the literature verification method were used to verify it.The molecular docking results were all good and above,and through literature verification,it was found that the core target enrichment analysis results had an action mechanism consistent with the previous research results of the research group;(7)the enrichment analysis of 237 targets in the core network of“Active Ingredients-Target-MI/RI" of Tan-Yu Tongzhi Prescription,GO analysis of 739 biological reaction processes and 131 KEGG signal pathways.2.Study on the molecular network mechanism of anti-MI/RI of the phlegm-removing traditional Chinese medicine group/the traditional Chinese medicine group for blood stasis-removing with Tan-Yu Tongzhi Prescription(1)The phlegm-removing traditional Chinese medicine group of Tan-Yu Tongzhi Prescription has 173 Chinese medicine ingredients,87 Chinese medicine active ingredients,and a total of 560 predicted targets;the traditional Chinese medicine group of blood stasis-removing has a total of 143 Chinese medicine ingredients and traditional Chinese medicine active ingredients 194.A total of 430 targets were predicted.(2)There are a total of 178 anti-MI/RI targets in phlegm-removing Chinese medicine group of Tan-Yu Tongzhi Prescription,and 140 core targets are obtained using the String database;Use the String database to obtain 113 core targets from a total of 155 anti-MI/RI targets in the Tan-Yu Tongzhi Prescription of blood stasis-removing Chinese medicine group.(3)The enrichment analysis of 140 core targets of anti-MI/RI in the phlegm-removing Chinese medicine group of Tan-Yu Tongzhi Prescription showed that there were 469 biological reaction processes by GO analysis and 114 KEGG signal pathways;the enrichment analysis of 113 core targets of anti-MI/RI in the blood stasis-removing Chinese medicine group of Tan-Yu Tongzhi Prescription showed that there was a total of 495 biological reaction processes by GO analysis and a total of 108 KEGG signal pathways.Conclusion1.The restart random walk algorithm based on the average shortest path bias proposed in this research can more accurately extract the core network of "active components of traditional Chinese medicine-target-MI/RI",which is also a reference provided in the application of this algorithm to the research of network pharmacology in the field of traditional Chinese medicine.2.There are 32 active ingredients of anti-MI/RI core Chinese medicines in Tan-Yu Tongzhi Prescription.The core Chinese medicines are 6 Chinese medicines including ginseng,chuanxiong and scallion white.3.Tan-Yu Tongzhi Prescription presents the characteristics of multi-component,multi-target,multi-signal pathways synergistic anti-MI/RI.The "inflammatory response" mechanism of Tan-Yu Tongzhi Prescription against MI/RI and the "negative regulation of apoptosis process" of the phlegm-removing group anti-MI/RI mechanism of Tan-Yu Tongzhi Prescription in this study are similar to the previous research results of the research group Coincide.In addition,The anti-MI/RI mechanism of Tan-Yu Tongzhi Prescription may be related to "PI3K-Akt signaling pathway" "TNF signaling pathway" "positive regulation of ERK1 and ERK2 cascade" "positive regulation of nitric oxi de biosynthesis process" and "MAPK cascade".The anti-MI/RI molecular network mechanism of the Phlegm-removing group of Tan-Yu Tongzhi Prescription may also be related to the "cAMP signaling pathway" and the anti-MI/RI molecular network mechanism of the blood-removing group of Tan-Yu Tongzhi Prescription may be related to the "HIF-1 signaling pathway"and "vascular endothelial growth factor signaling pathway".