| Angina pectoris in coronary heart disease is a serious health hazard,and the course of the disease is prolonged and difficult to cure,causing a serious health burden to the patient,family and society.The typical clinical manifestation of this disease is a heavy tightness or pain in the chest with a feeling of pressure and constriction,which belongs to the category of "chest paralysis and heart pain" and "true heart pain" in Chinese medicine,and the nature of the disease is mostly deficient and real.In this study,we used network pharmacology to construct a "drug-active ingredient-disease-target" network to predict and screen the effect of Yiqi Tongmai Decoction on the prevention and treatment of angina pectoris in coronary heart disease.In this study,we used network pharmacology to construct a "drug-active ingredient-disease-target" network to predict and screen the action targets and signaling pathways of Yiqi Tongmai Decoction for the prevention and treatment of stable angina pectoris in coronary heart disease.Objective:1 Predicting and screening the action targets and pathways of Yiqi Tongmai Decoction for the prevention and treatment of angina pectoris in coronary artery disease through network pharmacology2 Preliminary investigation on the protective effect and mechanism of Yiqi Tongmai Decoction on the heart of rats with myocardial ischemia through animal experiments.Methods:1 We selected TCMSP and BATMAN-TCM databases to screen the active ingredients of pulse Yiqi Tongmai Decoction,combined with SwissTargetPredicition database for target prediction,and selected Genecards and Disgenet databases to screen the targets related to angina pectoris of coronary heart disease,and constructed a "drug-active ingredient-disease-target" network for GO function and KEGG pathway enrichment analysis.2 The animal model of myocardial ischemia was made by ligating the anterior descending branch of coronary artery in rats,and the success of modeling was judged by postoperative electrocardiogram,and the rats were randomly divided into sham operation group,model group,Yiqi Tongmai group and Valsartan group.The effects of Yiqi Tongmai Decoction on cardiac function,structure and Ang Ⅱ level in rats after myocardial ischemia were observed by small animal cardiac ultrasound,tongue collection,HE staining,Elisa and Western Blot,and the predicted target and mechanism of action were verified based on network pharmacology.Results:1 Results of network pharmacological analysisThe main active ingredients of Yiqi Tongmai Decoction for the prevention and treatment of stable angina pectoris in coronary artery disease are:lignocaine and dousterol.The main targets of action involve STAT3,AKT1,MAPK3,MAPK1,PIK3CA and so on.The enrichment analysis of the pathways showed that the relevant signaling pathways are PI3K-Akt signaling pathway,AGE-RAGE signaling pathway and MAPK signaling pathway,etc.2 Animal experimental resultsThe ultrasound results showed that the left ventricular ejection fraction(EF)and fractional shortening(FS)of the rats in the Yiqi Tongmai groups increased compared with those in the model group(P<0.05);the hemodynamic results showed that the differences in LVSP values between the four groups were not statistically significant;compared with the sham-operated group,the LVEDP of the rats in the model group increased(P<0.05).LVEDP was increased in the model group compared with the sham-operated group(P<0.05),and decreased in the Yiqi and valsartan groups compared with the model group,with statistically significant differences(P<0.05);The values of+dp/dt max and-dp/dt max were lower in the model group compared with the sham-operated group(P<0.05,P<0.01),and the values of+dp/dt max and-dp/dt max were slightly higher in the Yiqi and valsartan groups compared with the model group,with no statistically significant differences.The rats’ heart structure and HE staining results showed that the heart tissue of the model group was obviously damaged,the myocardial cell gap was enlarged under the microscope,the cell arrangement was disordered,there were obvious inflammatory cell infiltration,the cell structure was blurred and cell edema appeared;the myocardial structure of the rats in the Yiqi Tongmai group and the valsartan group had different degrees of improvement compared with the model group,the myocardial fibers were more complete and the cell staining was relatively uniform;the tongue image The results showed that the stagnant tongue of the rats in the Yiqi and Valsartan groups was less stagnant than that of the model group.Elisa results indicated that Ang Ⅱ concentration in myocardial tissues of rats in the model group increased(P<0.01),and Ang Ⅱ levels in myocardial tissues of the Yiqi Tongchuang group and the valsartan group were reduced compared with the model group(P<0.05);p-PI3K/PI3K ratio in the model group decreased(P<0.01),and p-Akt/Akt ratio in the model group decreased,but the differences were not statistically significant(P>0.05);compared with the model group,the p-PI3K/PI3K protein ratio increased in the Yiqi and Valsartan groups(P<0.05),and the relative expression of p-Akt/Akt protein increased in the Yiqi and Valsartan groups,but the difference was not statistically significant(P>0.05)Conclusion:The results of network pharmacology prediction suggest that the main active ingredients of Yiqi Tongmai Decoction for the prevention and treatment of angina pectoris in stable coronary heart disease may be lignans and dousterols,and the main targets of action involve STAT3 and AKT1.The enrichment analysis of the related signaling pathways included PI3K-Akt signaling pathway,AGE-RAGE signaling pathway and MAPK signaling pathway.The experimental results confirmed that Yi Qi Tong Wei Tang could improve cardiac function,protect cardiomyocytes and reduce Ang Ⅱ level in myocardial ischemia model rats.The cardioprotective effect may be related to the activation of PI3K/Akt signaling pathway. |
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