Action Mechanism of Yangxin Tongmai Formula in Treating Coronary Heart Disease with Heart Qi Deficiency Syndrome Based on RNA Sequencing
Objective:Based on RNA sequencing technology,we screened the potential targets of Yangxin Tongmai Formula for treatment of coronary heart disease(CHD)with Heart Qi deficiency syndrome.Methods:Twenty-four SD rats were randomly divided into a con-trol group(9 rats)and a modeling group(15 rats),the latter of which used forceful swimming combined with isoprenaline injection to establish a model of CHD Heart Qi deficiency syndrome.The rats with successful modeling were randomly divided into the model group and the group of Nourishing Heart and Channel Formula(4.5 g·kg-1),and were gavaged continuously for 14 d.The serum cyclic a-denosine monophosphate(cAMP),atrial natriuretic peptide(ANP),and cardiac natriuretic peptide(CNP)levels of the rats were de-tected by ELISA,and HE staining was used to observe the rats'blood serum.The cardiac pathological morphology of rats was observed by HE staining.M-mode ultrasound was used to detect the cardiac function of rats,including left ventricular end-systolic dimensions(LVEDs),left ventricular end-diastolic dimensions(LVEDd),ejection fraction(EF)and cardiac function.ejection fraction(EF)and fractional shortening(FS).Differentially expressed genes were detected by RNA sequencing and analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).Protein-protein interaction(PPI)network was constructed by STRING da-tabase,and core genes were screened by Cytoscape software.Results:The rats in the modeling group were mentally unstable,accompa-nied by obvious symptoms of physical discomfort.The rats in the Yangxin Tongmai Formula group showed improved mental status and increased activity.There was no obvious abnormality in the electrocardiogram of rats in the blank group.The electrocardiogram of rats in the model group showed QRS wave widening,ST segment elevation and pathological Q waves.Compared with the blank group,the serum levels of cAMP and ANP were increased in the model group and decreased after treatment with Yangxin Tongmai Formula(P＜0.01).HE staining results showed that the myocardial transverse stripe was unclear,with degeneration and necrosis,and with inflammatory cell infiltration in the model group rats.The rats in the Nourishing Heart and Promoting Pulse Formula group showed mild myocardial fiber degeneration and connective tissue hyperplasia.Compared with the blank group,rats in the model group showed an increase in LVEDd and LVEDs,and a decrease in EF and FS(P＜0.01),which was reversed after treatment with Yangxin Tongmai Formula.Altogether 1 057 differentially expressed genes were identified by RNA sequencing among the three groups,which were enriched in biological processes such as cell cycle,chromosome segregation,and protein binding,as well as in pathways such as T cell receptor signaling path-way,Th17 cell differentiation,and Th1 and Th2 cell differentiation.Th2 cell differentiation and other pathways.5 core genes including Mcm7,Mcm4,Mcm6,Rfc3,Rfc5 were validated for their clinical value using ROC curve.Conclusion:Yangxin Tongmai Formula may play a role in the treatment of Heart Qi deficiency in CHD by regulating Mcm7,Mcm4,Mcm6,Rfc3 and Rfc5.
万方数据
维普
