| BackgroundCoronary heart disease is one of the diseases with the highest mortality rate in the world.Its incidence rate is high,the disease progresses rapidly,and its mortality rate ranks first in China.Under stress conditions such as ischemia and hypoxia,cardiomyocytes produce a large amount of reactive oxygen species,the peroxidation of polyunsaturated fatty acids intensifies,and toxic aldehydes are produced,triggering a "waterfall" cascade reaction,which in turn leads to cardiomyocyte apoptosis and inflammation,the occurrence of the reaction is an important pathological basis of the pathogenesis of myocardial infarction.Although percutaneous coronary intervention(PCI)can greatly reduce the mortality rate of patients,the recurrence of angina after myocardial infarction still seriously affects the quality of life of patients.Traditional Chinese medicine believes that coronary heart disease belongs to the category of chest pain and heart pain,and qi stagnation and blood stasis are common syndromes in clinical practice.Wenxin Decoction(WXT)is an effective prescription summed up by Professor Li Jun of Guang’anmen Hospital for many years and combined with the experience of famous old Chinese medicine practitioners.It is composed of 11 traditional Chinese medicines,including Astragalus mongholicus、Radix Pseudostellariae、Radix Paeonia、Ligusticum chuanxiong、Trichosanthes kirilou、Allium macrostemon、Pinellia ternata、cassia twig、turmeric、bombyx rigidis、Rhubarb.It has a significant effect on the treatment of recurrent angina after myocardial infarction.This study intends to explore the protective effect and molecular mechanism of WXT on cardiomyocytes through network pharmacology and rat myocardial infarction model.1.Discussion on the core target and mechanism of Wenxin Decoction in the treatment of coronary heart disease angina pectoris based on network pharmacologyObjective To explore the pharmacological mechanism of WXT in the treatment of angina pectoris after myocardial infarction by using network pharmacology methods,and to find the key targets and possible signaling pathways involved in the process,so as to lay a theoretical foundation for the research on the mechanism of WXT in the treatment of angina pectoris after myocardial infarction.Methods The Chinese medicine system pharmacology database and analysis platform(TCMSP)obtained the potential relevant targets of WXT Chinese medicine,and screened them from the human Mendelian disease database(OMIM),the drug database(Drugbank),and the human gene database(GeneCards)database.The target points of myocardial injury are intersected,and the interaction network diagram of the intersected target proteins is constructed based on the STRING database.According to the Cytoscape 3.9.1 software,the network of "key active ingredients of Wenxin Decoction-disease targets" was constructed,and the core targets were screened out.Using the Metascape platform to conduct GO and KEGG enrichment analysis on the"drug-disease" intersection targets,the signaling pathways that may be involved in the treatment of myocardial injury with qi deficiency and blood stasis type were screened out by Wenxin Decoction.Results A total of 173 intersection targets of Wenxin Decoction and myocardial injury were obtained,including interleukin-6(IL6),tumor necrosis factor(TNF),serine/threonine protein kinase(AKT1),interleukin-1(IL1B),TP53,CASP3,JUN,etc.KEGG enriched 205 signaling pathways,including cancer-related pathways(Pathways in cancer),lipid and atherosclerosis(Lipid and atherosclerosis),PI3K/Akt signaling pathway,MAPK signal pathways,etc.2.Mechanism of Wenxin Decoction on Myocardial Protection in Rats After Myocardial InfarctionObjective To observe the pharmacodynamic effect of WXT on rats with myocardial infarction by constructing a rat model of myocardial infarction,verify the protective effect of WXT on myocardial tissue after myocardial infarction,and explore its molecular mechanism.Methods The MI model of Wistar rats was established by ligation of left anterior descending coronary artery(LAD),and they were randomly divided into sham operation group(Sham,n=10),model group(MI,n=10),WXT low-dose group(WXT-L,n=10),WXT medium dose group(WXT-M,n=10),WXT high dose group(WXT-H,n=10),trimetazidine group(TMZ,n=10).The WXT group was given intragastric administration of traditional Chinese medicine,the TMZ group was given intragastric administration of positive medicine,and the rest groups were given intragastric administration of the same amount of normal saline.After continuous gavage for 4 weeks,small animal echocardiography was used to observe the changes in rat heart structure and function;hematoxylin-eosin(HE)and Masson(Masson)staining were used to evaluate rat myocardial histopathological changes and the degree of fibrosis;observe the ultrastructural changes of myocardial cells in the border area of myocardial infarction by transmission electron microscope;detect the apoptosis of rats in the border area of myocardial infarction by TUNEL staining;detect the expression levels of inflammatory factors TNF-α in rat serum by enzyme-linked immunosorbent assay(Elisa);the mRNA and protein expressions of PI3K,Akt,NF-κB in myocardial tissue were detected by Western blot.Results 1.Compared with the model group,WXT can significantly improve the cardiac function level of MI rats,significantly increase the levels of LVEF,LVFS,and LVAWs(P<0.01),and reduce LVIDd,LVIDs,and LVVd(P<0.01),the change was positively correlated with drug concentration.2.Myocardial histopathological examination shows that after WXT intervention,it can effectively alleviate pathological changes such as myocardial cell arrangement disorder and inflammatory cell infiltration in MI rats.Through Masson staining,it is found that WXT can inhibit myocardial fibrosis and improve ventricular remodeling,the difference was statistically significant.3.The results of transmission electron microscopy showed that the mitochondrial outer membrane was complete and the cristae were dense in the rats in the Sham group,and the myocardial mitochondria in the MI group were abnormal in shape,reduced in number,cristae disordered and matrix swollen.After WXT intervention,the above-mentioned changes in the number and structure of mitochondria can be reversed to a certain extent.4.The results of TUNEL staining showed that compared with the MI group,with the increase of WXT concentration,the proportion of apoptotic cells in the border area of myocardial infarction was significantly reduced,and the difference was statistically significant.5.The results of Elisa showed that compared with the model group,TNF-α in the serum of MI rats was significantly reduced after WXT intervention,and the difference was statistically significant.6.WXT can significantly increase the expression of PI3K,Akt protein in myocardial tissue,and reduce the expression level of NF-κB,the results are statistically significant.Conclusion Compared with the model group,WXT can effectively relieve myocardial injury after myocardial infarction in rats,restore cardiac function,inhibit myocardial inflammatory response,inhibit myocardial fibrosis,delay ventricular remodeling,and improve the number and structure of mitochondria in myocardial cells,reducing cell apoptosis,this phenomenon may be related to the fact that WXT can reduce the level of myocardial cell apoptosis after myocardial injury through the PI 3 K/Akt/NF-κB signaling pathway.As a methodological model,network pharmacology can predict the core targets and possible signaling pathways of traditional Chinese medicine compound ingredients in treating diseases. |
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