Synchronous Module Study On The Pharmacodynamics Of Danhong Injection In The Treatment Of Stable Angina Pectori

Objective:This study integrates synchronization theory with modular pharmacology,takes single target and multiple targets,namely genes and modules,as the research objects,and constructs an evaluation method for the dynamic synchronization relationship between single genes and modules with changes in curative effect.By quantifying the synchronization relationship between modules in the stable angina pectoris molecular network intervention by Danhong injection,explore the influence of synchronization phenomena on the transmission of biological information,look for changes in pharmacological functions brought about by the evolution of synchronization genes and synchronization modules,and clarify the synergistic mechanism of Danhong injection’s pharmacodynamic response.Methods:In this study,the pharmacodynamic evaluation and whole blood genome sequencing of Danhong injection in the treatment of chronic stable angina pectoris were carried out,and the population was divided into groups based on the efficacy results,and analyzed from two aspects:(1)Gene synchronization analysis:by calculating the Pearson correlation of the transcriptional expression of the two genes,and whether the correlation direction is consistent with the curative effect change direction as the screening condition,qualitative analysis was carried out on the positive and negative gene pairs that interact with each other with the change of curative effect grade;(2)Module Synchronization analysis:construct a gene co-expression network,and then divide the modules.By extracting module features of multiple dimensions,constructing trajectory data that changes with the curative effect level,and using the entropy method to perform weighting integration operations on the module features to calculate the synchronization between the modules.Use 0.8 and-0.3 as the filter threshold of the synchronization module respectively.The synchronization score greater than 0.8 is regarded as a synchronization module,which is a positive synchronization module,and the synchronization score less than-0.3 is an anti-synchronization module.Finally,enrichment analysis on the synchronization module pairs were performed,and screen the hub nodes in the synchronization module using the degree centrality and betweenness centrality.Based on this,the biological function of the pharmacodynamic response synchronization module of Danhong injection in the treatment of stable angina pectoris was analyzed.Results:1.Analysis of the curative effect of Danhong injection:using the complete condition method to fill in the data multiple times,after 30 days of treatment,the improvement rate of angina pectoris(AF)in the Danhong test group was 52.41%and that of the control group was 39.62%.The difference in the improvement rate between the two groups was statistically significant(P=0.0003),and the subjects were divided into invalid group,improved group,effective group and markedly effective group according to AF,with 20,6,7,8 people in each group,respectively.2.Identification and enrichment analysis of single gene synchronization pairs:Pearson correlation coefficients between genes of different therapeutic groups are used to determine gene synchronization.On the 14th and 30th days,1021,1299 positive-synchronous gene pairs and 25,203 anti-synchronous gene pairs were identified respectively.Both positive and anti-synchronous gene pairs have a regulatory effect on ribosomal pathways,and positive-synchronous gene pairs are also involved in pathways such as oxidative phosphorylation.3.Recognition of synchronization module pairs:as the curative effect level changes,multidimensional module trajectory data entropy values are used to integrate synchronization scores to evaluate the synchronization relationship between modules,and a total of 8 pairs of synchronization modules are identified using threshold screening,of which 7 pairs of positive synchronization modules and 1 pair of anti-synchronization modules.4.Identification of main modules:build an interaction network between modules,and evaluate the rank sum comparison module of a variety of network topology parameter generation modules.The results show that module 38 is the core module in the network,which is mainly involved in the regulation of leukocyte chemotaxis,Neutrophil activation,NK cell activation and other biological processes.5.The screening results of the core nodes in the synchronization module show that HNRNPN1,TNFRSF1 A,HSPA1 A,and FOS are the core nodes of the No.1,module No.38,and No.28 modules in the positive synchronization module pair,and the synchronization is based on the core node.The modules jointly participate in the MAPK signaling pathway,protect the myocardium,and resist cell apoptosis.This may be the potential mechanism of Danhong injection in the treatment of stable angina pectoris.Conclusion:1.By calculating the Pearson correlation of the transcription and expression of the two genes,and combining whether the direction of the correlation and the direction of the curative effect change are the same as the screening conditions,a judgment method for identifying synchronized gene pairs is established.2.By extracting the module features of 5 dimensions,and using the entropy method to perform weighted integration operation on the dynamic trajectory data that changes with the curative effect grade sequence,a method for quantitatively evaluating the synchronization relationship between the modules is established.3.This study revealed the potential pharmacological action mechanism of Danhong injection on the MAPK signaling pathway through multiple targets through the synchronous module study of pharmacodynamic response.