| Fuxin decoction is composed of Aconite,Astragalus and Lepidii.It is the basic and effective prescription for treating chronic heart failure by Professor,affiliated Hospital of Shandong University of traditional Chinese Medicine.This paper is divided into three interrelated parts.The first part uses Meta analysis method to compare the curative effect of Fuxin decoction combined with western medicine in the treatment of chronic heart failure directly and indirectly.The second part is based on the network pharmacological method to explore the possible mechanism of Fuxin decoction in the treatment of heart failure.The third part uses the animal experiment method to study the mechanism of mitochondrial permeability transition hole in the treatment of heart failure rats with Fuxin decoction.Section 1: Direct and Indirect Comparison of the Efficacy of Fuxin Decoction Combined with Western Medicine Therapy in the Treatment of Chronic Heart Failure Based on Meta AnalysisObjective: The curative effect of Fuxin decoction in treatment of chronic heart failure was directly compared with conventional Meta analysis and indirectly compared with other prescriptions of warming yang,supplementing qi and excreting water by network Meta analysis.Methods: The computer associating with manual method was used to search the common databases at home and abroad,to screen out the relevant documents that met the inclusion criteria,to evaluate the literature quality,to use Rev Man5.3 software for head-to-head Meta analysis,and to use Win BUGS14 software for network Meta analysis.Results: Finally,15 randomized controlled clinical trials were included in the study,including 14 Chinese and 1 foreign language literature,including 1412 patients,648 cases in the control group and 764 cases in the observation group.The results of head-to-head Meta analysis showed that compared with western medicine control group,Fuxin decoction group was significantly better in TCM syndrome(P<0.0001),NYHA cardiac function grade(P<0.0001),left ventricular ejection fraction(LVEF)(P<0.0001),and the plasma BNP level(P<0.0001),and was statistically significant.Network Meta analysis showed that there was no significant difference between Fuxin decoction group and non-Fuxin decoction group.However,in terms of TCM syndrome,NYHA cardiac function grade and plasma BNP level,the curative effect ranked probability of Fuxin decoction group was significantly higher than that of non-Fuxin decoction group,but in left ventricular ejection fraction was not as good as the observation group of non-Fuxin decoction.Conclusion: Fuxin decoction combined with western medicine in the treatment of chronic heart failure in TCM syndrome evaluation,cardiac function grade,left ventricular ejection fraction,plasma BNP level is better than the western medicine control group,showing a good curative effect.In the TCM syndrome evaluation,NYHA cardiac function classification,plasma BNP level,Fuxin decoction observation group with greater probability was better than the non-Fuxin decoction observation group,although there is no statistical difference.We still need more related research to participate in the observation.Section 2: Molecular Mechanism Analysis of Heart Failure Treated by Fuxin Decoction Based on Network PharmacologyObjective: To analyze and predict the mechanism of Fuxin decoction in treating heart failure based on network pharmacology.Methods: The active components,action targets and disease targets of heart failure were obtained by using network pharmacological tools and methods.The key targets and the core cluster of Fuxin decoction acting on heart failure were found out,the related signal pathways were analyzed,and possible molecular mechanisms were explored.Results: Fuxin decoction is predicted to contain 53 blood-entering components,covering 224 targets,among which 94 direct targets act on heart failure.Through network extension and integration,a PPI network consisting of 675 nodes and 3085 kinds of relationships was obtained.The most important 255 core targets and one core cluster were selected.The core cluster was composed of 56 nodes and 297 interaction relationships.KEGG pathway analysis showed that HSP90,PI3 K,AKT,MAPK-related genes,adenylate cyclase and guanine nucleotide binding protein(G protein)were the most important,closest and most likely sites for Fuxin decoction to act on heart failure.Conclusion: The mechanism of Fuxin decoction in the treatment of heart failure is related to ?ARs-G protein-adenylate cyclase,PI3K-Akt signaling pathway and HSP90,MAPK.Section 3: Study on the Mechanism of Mitochondrial Permeability Transition Hole in Rats with Heart Failure Treated by Fuxin DecoctionObjective: To observe the relationship between the therapeutic effect of Fuxin decoction and the opening degree of mitochondrial permeability transition pore(mitochondrial permeability transition pore,m PTP)in rats with heart failure,and to explain the mechanism of Fuxin decoction in treating heart failure.Methods: The blank control group,heart failure model group,western medicine control group and Fuxin decoction group were established randomly with 20 rats in each group.The model of heart failure was established by intraperitoneal injection of adriamycin into Wistar rats.After 6 weeks of intervention,the mortality rate,plasma BNP value were estimated,cardiac function were measured by color Doppler echocardiography and the changes of A540 absorbance of myocardial mitochondria under the action of m PTP open inducer were measured to evaluate the degree of m PTP opening of myocardial mitochondria in each group.To observe the correlation between the measured values of Fuxin decoction group and the opening degree of myocardial mitochondrial permeability transition pore.Results :Compared with the model group,Fuxin decoction group was significantly better in the mortality rate(P<0.01),the indexes of cardiac color Doppler ultrasonography[LVEDD(P<0.01),LVEDS(P<0.01),FS(P<0.01),EF(P<0.01)],serum BNP(P<0.01)and the ratio of absorbance of m PTP(P<0.01).Compared with the western medicine control group,Fuxin decoction group also had significant curative effect in the mortality rate(P<0.05),the indexes of cardiac color Doppler ultrasonography [LVEDD(P<0.01),LVEDS(P<0.01),FS(P<0.01),EF(P<0.01],serum BNP(P<0.01)and the ratio of absorbance of m PTP(P<0.01)].In Fuxin decoction group,there was no significant correlation between LVEDD value(P=0.028)and m PTP(?A540/initial),but LVEDS value(P<0.05)and serum BNP(P<0.05)were negatively correlated with ?A540/initial value of m PTP,The FS(P<0.01)and EF(P<0.01)values of cardiac color Doppler were positively correlated with the value of ?A540/initial of m PTP.Conclusion: Fuxin decoction has a good effect in improving mortality,serum BNP and heart color Doppler values on heart failure rats,and can effectively improve myocardial mitochondrial m PTP permeability in rats with heart failure,and there is a correlation between them.It is concluded that Fuxin decoction may improve the myocardial mitochondrial energy metabolism and myocardial apoptosis by improving the permeability of myocardial mitochondrial m PTP in rats with heart failure,so that Fuxin decoction can achieve therapeutic effect. |
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