| With the increase of life pressures and work pressures,depression after myocardial infarction is becoming more and more prevalent in the population.According to data released by the World Health Organization in 2017,the incidence of depression in patients with myocardial infarction is about 40%,much higher than that in the general population(5%to 10%).Depression is an independent risk factor for the occurrence and development of myocardial infarction.Studies have reported that in people with depression,the incidence of serious complications such as malignant arrhythmia,severe heart failure and shock after MI and the death rate after percutaneous coronary intervention(PCI)are significantly higher than that of non-depressed people.Therefore,the treatment of depression after myocardial infarction should not be neglected.At present,the treatment of western medicine is mainly based on basic drugs after myocardial infarction combined with antidepressants,but this treatment has problems such as poor compliance,can induce fatal arrhythmia,and increase the incidence of adverse cardiovascular events.Therefore,there is no safe and effective treatment method Myocardial infarction is classified as "True Heart Pain",while depression is classified as Depression Disease".Traditional Chinese medicine believes that depression after myocardial infarction should be treated based on "double heart therapy",namely,"heart of blood" and heart of spirit" should be treated at the same time.Shuangxin Prescription is the effective Prescription summarized by our team in clinical practice.Preliminary clinical studies have found that Shuangxin Prescription has certain efficacy in the treatment of depression after myocardial infarction,but its specific mechanism is not clear.Network pharmacology can systematically analyze the mechanism of action of drugs in the treatment of diseases,explore new indications of existing drugs or predict new drug targets,which is consistent with the concept of wholism of Chinese medicineStudy 1 A Network Pharmacological Study of Shuangxin Prescription in the Treatment of Depression after Myocardial InfarctionObjective:To explore the mechanism of Shuangxin Prescription in the treatment of depression after myocardial infarction based on network pharmacologyMethods:The active ingredients and corresponding targets of Shuangxin Prescription were obtained by TCMSP database,and the relevant targets of myocardial infarction and depression were collected by GeneCards and PharmGKB database and then integrated.and the potential target of Shuangxin Prescription was obtained after the intersection of targets of drug and disease.The drug-component-target-disease network was constructed using Cytoscape3.8.2.PPI network was analyzed using String database,and GO and KEGG enrichment analysis was performed using David V6.8 database.Results:88 effective components,89 potential targets,and 10 core targets of Shuangxin Prescription.229 biological process items,and 34 KEGG signaling pathways were obtained Mediated by multiple signaling pathways such as HIF-1,PI3K-AKT,the multiple active ingredients in Shuangxin Prescription have a cardioprotective effect,can treat myocardial infarction and improve prognosis by anti-apoptosis,anti-inflammation and anti-oxidative stress reaction,promoting angiogenesis in the heart after infarction,and improves depression by inhibiting oxidative stress damage of neurons,reducing inflammation-mediated cytotoxicity and neuronal deathConclusion:Shuangxin Prescription mainly plays a role in the treatment of depression after myocardial infarction through multi-target and multi-pathway.This study provides a basis and direction for further research on the mechanism of Shuangxin Prescription in the treatment of depression after myocardial infarctionStudy 2 To Explore the Mechanism of Shuangxin Prescription in the Treatment of Depression After Myocardial Infarction in Rats Through PI3K/AKT Signaling PathwayObjective:To explore the mechanism of Shuangxin Prescription in the treatment of depression after myocardial infarction in rats Through PI3K/AKT signaling pathwayMethods:Ligation of left anterior descending coronary artery combined with chronic unpredictable mild stimulation(CUMS)was used to establish a rat model of depression after myocardial infarction.Rats were randomly divided into 4 groups:blank group,sham group,model group and Shuangxin Prescription group.Cardiac function was evaluated by echocardiography and structural changes of the heart and hippocampus were observed by pathological staining.Open field test and sugar water test were used to evaluate the depression status of rats.The levels of DA and NE were detected by ELISA.The expressions of PI3K and p-PI3K,AKT and p-AKT,GSK3? and p-GSK3?,Bcl-2 and Bax,and cleaved-Caspase3(c-Caspase3)in the marginal zone of myocardial infarction and hippocampus were detected by Western blot.Results:Echocardiography showed that there was no significant difference in left ventricular end diastolic diameter(LVIDd),left ventricular end systolic diameter(LVIDS),ejection fraction(EF)and fraction shortening(FS)between the blank group and the sham group(P>0.05);EF and FS in the model group were lower than those in the blank group,while LVIDd and LVIDS were higher than those in the blank group,the differences were statistically significant(P<0.05);EF and FS in the Shuangxin Prescription group were higher than those in the model group,while LVIDd and LVIDS were lower than those in the model group,the differences were statistically significant(P<0.05).The results of the sugar water test showed that there was no statistical difference in the sugar water preference rate between the blank group and the sham group before giving medicine(P>0.05),the preference rate of sugar water in model group and Shuangxin Prescription group was lower than that in blank group,and the difference was statistically significant(P<0.05);After giving medicine,there was no statistical difference between the blank group and the sham group(P>0.05),the preference rate of sugar water in model group was lower than that in blank group,and the difference was statistically significant(P<0.05),the preference rate of sugar water in the Shuangxin Prescription group was higher than that in the model group,and the difference was statistically significant(P<0.05).In the open field test,the total distance of horizontal movement and vertical movement showed no statistical difference between the blank group and the sham group before administration(P>0.05).the model group and the Shuangxin Prescription group were lower than the blank group,and the difference was statistically significant(P<0.05);After giving medicine,there was no statistical difference between the blank group and the sham group(P>0.05),the model group was lower than the blank group,and the difference was statistically significant(P<0.05),the Shuangxin Prescription group was higher than the model group,and the difference was statistically significant(P<0.05).The results of HE pathological staining of the heart showed that in the blank group,the myocardial tissue was compact,the fibers were arranged neatly,the staining was uniform,the morphology of myocardial cells was regular,and the morphology of the nucleus was normal.There was no obvious abnormality in the sham operation group.In the model group,the ventricular wall became thinner,the myocardial cells in the edge area of infarction were denatured and necrotic,and some of them were replaced by connective tissue,and inflammatory cells were infiltrated.The degeneration and necrosis of cardiomyocytes and infiltration of inflammatory cells were reduced in the Shuangxin Prescription group.The results of Haimani's pathological staining showed that the hippocampal neurons in the blank group and the sham group were rich in layers,orderly in arrangement,complete in capsule,normal in morphology and no cell necrosis was observed.The level and number of hippocampal neurons in model group were reduced,and the cell arrangement was sparse.Compared with the model group,hippocampal neurons in the drug administration group were more hierarchical and regular in cell morphology.ELISA results showed that there were no significant differences in dopamine(DA),noradrenaline(NE)between the blank group and the sham group(P>0.05);DA and NE in the model group were lower than those in the blank group,and there were statistically significant differences between groups(P<0.05);DA and NE in the Shuangxin Prescription group were lower than those in the blank group,and there were statistically significant differences between the two groups(P<0.05).Western blot of the hippocampus showed that there was no significant difference in PI3K,AKT and GSK3? among the groups(P>0.05);p-PI3K,p-AKT,p-GSK3?,there was no significant difference between the blank group and the sham group(P<0.05),and there was statistical difference between the model group and the blank group(P<0.05),there was a statistical difference between the Shuangxin Prescription group and the model group(P<0.05);Bax,Bcl-2,c-Caspase3,there was no statistical difference between the blank group and the sham group(P>0.05),and there was statistical difference between the model group and the blank group(P<0.05),there was a statistical difference between the Shuangxin Prescription group and the model group(P<0.05).Western blot of the marginal zone of myocardial infarction showed that there was no significant difference in PI3K,AKT and GSK3? among all groups(P>0.05);p-PI3K,p-AKT,p-GSK3?,there was no significant difference between the blank group and the sham group(P<0.05),and there was statistical difference between the model group and the blank group(P<0.05),there was a statistical difference between the Shuangxin Prescription group and the model group(P<0.05);Bax,Bcl-2,c-Caspase3,there was no statistical difference between the blank group and the sham group(P>0.05),and there was statistical difference between the model group and the blank group(P<0.05),there was a statistical difference between the Shuangxin Prescription group and the model group(P<0.05).Conclusions:Shuangxin Prescription may be mediated by PI3K/AKT signaling pathway to play an anti-apoptosis effect on cardiomyocytes and hippocampal neurons,and then effectively improve cardiac function and depression in rats. |
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