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Study On The Protective Effect Of Huangjin Xingqi Tongmai Formula On Myocardial Injury After Myocardial Infarction And The Regulatory Effect Of PI3K/AKT1 Signaling Pathway

Posted on:2024-08-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:B Y PangFull Text:PDF
GTID:1524307112483694Subject:Internal medicine of traditional Chinese medicine
Abstract/Summary:PDF Full Text Request
Objective: This study makes a thorough inquiry the effect of curcumin and traditional Chinese medicine for Huangjin Xingqi Tongmai Formula with Curcumae Longae Rhizoma and Curcuma wenyujin as the monarch drugs on the intervention of acute myocardial infarction and its possible mechanism,through data mining,network analysis,clinical trials and basic experiments.Methods:1.Clinical trialsThe patients with acute myocardial infarction with syndrome of qi stagnation and blood stasis were included.Randomized grouping after inclusion.In the experimental group,the traditional medicine was supplemented with the Huangjin Xingqi Tongmai Formula,which uses turmeric and curcuma as the monarch drugs.The clinical symptoms before and after treatment were evaluated using the Seattle Angina Pectoris Observation Scale and Symptom Rating Scale;CK-MB,Tn I,and NT-pro BNP were measured before and after treatment;Before and after treatment,LVEF,LVEDD,LVESD,LVFS and other cardiac function indicators were tested and compared.2.System evaluation and mate analysisRetrieve the relevant research of curcumin intervention on rat or mouse myocardial infarction model in rodents through database system,and extract relevant data.The meta-analysis was performed independently for each outcome indicator.We used risk assessment tools to evaluate the quality of research methods before conducting meta-analysis.3.Network pharmacology and molecular dockingUse the database to predict the action targets of curcumin and myocardial infarction respectively.Use Venn online software to obtain common targets of curcumin and myocardial infarction.The protein-protein interaction network was constructed through Cytoscape 3.9.1 to screen core targets.For rich analysis of Go and KEGG,we use Metascape database.Finally,we use Auto Dock software to conduct molecular docking between the core target and curcumin.4.Basic experimentThe electrocardiogram test of rats in the model group showed that the ST segment of lead II was elevated upward with intermittent ventricular tachycardia.The trend of ST segment elevation in each dose group of Huangjin Xingqi Tongmai Formula was significantly lower than that in the model group,and the arrhythmia in the electrocardiogram of the high-dose group was significantly improved.The concentrations of CK-MB,LDH,and MDA in the model group were significantly higher than those in the blank group,while the concentrations of SOD were significantly decreased.However,the changes in various indicators in the dose group were just the opposite,with the concentrations of CK-MB,LDH,and MDA decreased and the concentration of SOD increased in each dose group.Based on this analysis,the Huangjin Xingqi Tongmai Formula,which uses turmeric and Yujin as the monarch drugs,can promote the expression of p-PI3 K and p-AKT1 proteins in rats with myocardial infarction.Results:1.Clinical trialsThe Huangjin Xingqi Tongmai Formula with Curcumae Longae Rhizoma and Curcuma wenyujin as the monarch drugs can improve the degree of stable state of angina pectoris,physical activity limitation,angina pectoris attack and treatment satisfaction of patients with myocardial infarction,but has no significant impact on the degree of disease cognition.The Huangjin Xingqi Tongmai Formula with Curcumae Longae Rhizoma and Curcuma wenyujin as the monarch drugs can improve the angina pectoris in myocardial infarction patients.In the aspect of cardiac color Doppler ultrasound detection,Huangjin Xingqi Tongmai Formula can reduce LVEDD and LVESD of no-PCI patients with myocardial infarction,and improve LVFS and LVEF.2.System evaluation and mate analysisA comprehensive literature search was conducted in each database,according to the inclusion and exclusion criteria developed previously,24 studies were included after screening.The results showed that curcumin could reduce the levels of CK-MB,CK,LDH and MDA in myocardial infarction model;It can reduce SBP,DBP,LVEDP,LVW/BW,apoptosis index,LVEDD,LVESD and myocardial infarction area,and increase LVEF,LVFS,+dp/dtmax and-dp/dtmax;Besides it shows no significant effect on the content of SOD and heart rate.3.Network pharmacology and molecular dockingA total of 64 curcumin action targets,4852 targets related to myocardial infarction and44 cross targets were found in network pharmacology.The core targets of curcumin acting on myocardial infarction were screened through PPI network diagram,including AKT1,STAT3,EGFR,EP300,GSK3 B,etc.We conducted KEGG pathway enrichment.KEGG enrichment results involve PI3K-Akt and other signal pathways.Molecular docking showed that the core targets including AKT1,STAT3,EGFR,EP300,GSK3 B have good binding ability with curcumin.PI3K/AKT1 signal pathway may be related to the effect of curcumin on myocardial infarction.4.Basic experimentThe electrocardiogram test of rats in the model group showed that the ST segment of lead II was elevated upward with intermittent ventricular tachycardia.The trend of ST segment elevation in each dose group of Huangjin Xingqi Tongmai Formula was significantly lower than that in the model group,and the arrhythmia in the electrocardiogram of the high-dose group was significantly improved.The concentrations of CK-MB,LDH,and MDA in the model group were significantly higher than those in the blank group,while the concentrations of SOD were significantly decreased.However,the changes in various indicators in the dose group were just the opposite,with the concentrations of CK-MB,LDH,and MDA decreased and the concentration of SOD increased in each dose group.Based on this analysis,the Huangjin Xingqi Tongmai Formula,which uses turmeric and Yujin as the monarch drugs,can promote the expression of p-PI3 K and p-AKT1 proteins in rats with myocardial infarction.Conclusion:1.Clinical trialsThe Huangjin Xingqi Tongmai Formula,which uses turmeric and Yujin as the monarch drugs,can improve the clinical symptoms and treatment satisfaction of patients with myocardial infarction,and can improve the structural changes and cardiac function of the heart in patients with myocardial infarction.2.System evaluation and mate analysisCurcumin acts on rodent models of myocardial infarction such as rats and mice,which can alleviate myocardial injury and oxidative stress,improve the diastolic and contractile abilities of the ventricles,and reduce myocardial cell necrosis and apoptosis.3.Network pharmacology and molecular dockingThe core targets of curcumin acting on myocardial infarction were screened through PPI network diagram,including AKT1,STAT3,EGFR,EP300,GSK3 B,etc.PI3K/AKT1 signal pathway may be related to the effect of curcumin on myocardial infarction.4.Basic experimentHuangjin Xingqi Tongmai Formula with Curcumae Longae Rhizoma and Curcuma wenyujin as the monarch drugs contributes to the protection of myocardium and cardiac function in rats with myocardial infarction.The mechanism of Huangjin Xingqi Tongmai Formula with Curcumae Longae Rhizoma and Curcuma wenyujin as the monarch drugs may be related to the up-regulation of PI3K/AKT1 signal pathway.
Keywords/Search Tags:Huangjin Xingqi Tongmai Formula, Curcumin, myocardial infarction, Meta analysis, Network pharmacology, molecular docking
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