Study On Action Mechanisms And Material Basis Of "Psyco-Cardiological" Effect Of Xinkeshu Tablets

Objective: To excavate the theoretical basis of“psycho-cardiological ” effect of Xinkeshu tablets.And experiments were done to investigate the targets and pathway of Xinkeshu tablets for the treatment of“psychocardiological ”diseases and screen the active components based on the theoretical research.Methods:1.The theoretical excavation of “psycho-cardiological ” effect:The prescription rules for treating “psycho-cardiological ”with Traditional Chinese Medicine were analyses and then the efficacy and safety of Xinkeshu tablets for curing cardiovasular patients with anxiety and depression were systematically reviewed.2.The network pharmacology research of “psycho-cardiological ” effect:The “components-targets”network of Xinkeshu tablets and “diseasetargets”network of coronary heart disease,anxiety,depression were established.The targtes of “psycho-cardiological ”effect were screened and the pathway were enrichmently analysed.3.Effect and targets of Xinkeshu tablets on myocardial ischemia rats: Acute and chronic myocardial ischemia model were made to evaluate the therapeutical effects of Xinkeshu tablets.The anti-ischemic mechanism were studied with detecting the expression level of MMP2,MMP9,PI3 K and AKT in myocardium.4.Effect and targets of Xinkeshu tablets on depression rats:Chronic unpredicted mild stress model was established to explored the effect of Xinkeshu tablets on depressive behavior.The anti-depressive mechanism were studied with detecting the contents of amine neurotransmitter in serum and expression level of DRD1,DRD2,ADRA1 A and 5HTR1 A in hippocampus.5.Effect and targets of Xinkeshu tablets on ischemic-depression rats:The ischmic-depression model was established to study the curing effect of Xinkeshu tablets,and then the mechanims were discussed preliminarily.6.Anti-myocardial ischemia active parts screening of Xin Keshu: Different polar parts were extracted from the total extract of Xin Keshu with different solvents,and myocardial ischemia activity was screened with a myocardial ischemia hypoxia cell model.Results:1.Xinkeshu Tablet is effective and safe in treating coronary heart disease with anxiety and depression.2.The multi-components of Xinkeshu Tablets can act synergistically on multiple targets associated with coronary heart disease and anxiety and depression to exert double-heart effects through multiple pathways.The calcium signal pathway is a common pathway for the treatment of coronary heart disease and anxiety and depression.3.Myocardial infarction rate in rats with acute myocardial ischemia and the serum myocardial enzyme activity in acute and chronic myocardial ischemia rats can be reduced by Xinkeshu Tablets.These effects attribute to the down-regulation of myocardial MMP2,MMP9,and upregulation of PI3 K and AKT.4.The forced swimming time can be reduced by Xinkeshu Tablets,while sugar consumption and open field test scores increased.Increasion of serum monoamine neurotransmitters can be detected in rats treated with Xinkeshu Tablets,and the m RNA expression of DRD1,DRD2,and ADRA1 A in hippocampus rised.5.Xinkeshu Tablets can improve the myocardial injury and depression behavior in myocardial ischemia-stress model rats,and its mechanism is related to the regulation of MMP2,MMP9,DRD1,ADRA1 A expression.6.The n-butanol parts of total extract of Xin Keshu can inhibit myocardial cell death caused by anoxia and impove the cell viability.Conclusion: Xinkeshu Tablet can improve ischemia and protect myocardial injury caused by ischemia.It can obviously treat ischemia-induced depression and depression alone.Its anti-ischemic myocardial effect was associated with down-regulation of MMP2 and MMP9 expression and up-regulation of PI3 K and AKT expression in myoocardium while the anti-depressant effect was related with up-regulation of m RNA expression levels of DRD1,DRD2,ADRA1 A and ADRA2 A in hippocampus.The n-butanol part is the main active part of Xinkeshu Tablet for treating myocardial ischemia.