Research On The Anti-Arrhythmic Activity And Mechanism Of PPT Drops Based On Proteomics And Metabolomics

Cardiovascular diseases are currently at the top of the list of causes of death for people.Arrhythmias are a common clinical phenomenon,with main symptoms such as accelerated heartbeat,slowing down,and shortness of breath.Severe cases can lead to sudden death.Among them,arrhythmia mainly includes two types:tachycardia and bradycardia.In clinical practice,tachyarrhythmia is the most common type,and the main types are sinus,atrial,and ventricular tachycardia.In recent years,the incidence rate of arrhythmias in China has gradually increased,and tachyarrhythmia accounts for a large proportion of clinical patients,which has seriously endangered human health and quality of life.Many studies have shown that natural drugs have significant effects in the prevention and treatment of tachyarrhythmia,which has attracted the attention of researchers.Protopanaxatriol（PPT）is a metabolite of ginsenosides,and is a saponin of the ginsenoside group Re,Rf,Rg1,Rg2,Rh1.It has been found to have various biological activities such as anti myocardial ischemia,anti myocarditis,protection of vascular endothelial cells,protection of the nervous system,antioxidant,anti-inflammatory,and so on,which plays an important role in the prevention and treatment of cardiovascular diseases.Among them,there are literature reports that Re,Rf,Rg1,and Rg2 have regulatory effects on tachyarrhythmia,and their effects are closely related to the antioxidant and other PPT biological activities mentioned above.Therefore,in this paper,barium chloride（Ba Cl₂）is selected to establish a tachyarrhythmia model to carry out relevant research on the effects of PPT drop pills on tachyarrhythmia.Our research group has been conducting research on PPT for many years,and has found that it has biological activity in anti cardiovascular disease.Therefore,based on the review of the pathogenesis,model establishment,metabolomics,and proteomics research progress of tachyarrhythmia,this paper further evaluated the therapeutic effect of PPT dropping pills on tachyarrhythmia by establishing a rat model of barium chloride tachyarrhythmia,and conducted the first study on the mechanism of PPT dropping pills’anti tachyarrhythmia action from the perspective of proteomics and metabolomics,To provide reliable scientific basis for natural drug PPT in preventing and treating arrhythmia diseases.The achievements of the thesis are as follows:1.Effects of PPT dropping pills on arrhythmia induced by barium chloride in ratsA rat model of arrhythmia was established by injecting barium chloride into the tail vein.The anti tachyarrhythmia effect of PPT dripping pills was evaluated using rat electrocardiogram,blood SOD,MDA,and key enzymes in heart tissue as indicators.The results showed that in the electrocardiogram,the high dose group of PPT dropping pills had a significant regulatory effect on the barium chloride induced model,which could prolong its onset time and shorten its duration;In the measurement of relevant biochemical indicators,PPT at various doses can significantly reduce the content of MDA in serum;Increase the level of SOD（P<0.05）;The levels of Na2+-K+-ATPase and Ca2+-Mg2+-ATPase were significantly increased（P<0.05）.In addition,the high dose group of PPT could significantly delay the occurrence of arrhythmia（P<0.05）.The results suggest that PPT dropping pills have a significant regulatory effect on tachyarrhythmia induced by barium chloride in rats.2.A metabonomic study of serum and cardiac tissue in ratsUsing a non-target metabonomic technique based on UPLC-Q/TOF-MS,we detected the changes of metabolites in rat serum and heart tissue,and explored the biomarkers and metabolic pathways closely related to the effect of PPT dropping pills on tachyarrhythmia.The results showed that seven different metabolites,including arachidonic acid and lysophosphatidylcholine,were identified from serum and cardiac tissue,and they involved seven metabolic pathways,including glycerol phospholipid metabolism,retinol metabolism,ether lipid metabolism,and arachidonic acid metabolism.Some literature reported that the occurrence of tachyarrhythmia was closely related to these pathways,and lipid metabolism was found in the result processing,Arachidonic acid metabolism is the main metabolic pathway,suggesting that the regulatory effect of PPT dropping pills on tachyarrhythmia may be related to antioxidant capacity,providing a scientific basis for clarifying the mechanism of PPT dropping pills’anti arrhythmia effect.3.Study on proteomics of rat heart tissueUsing Label free quantitative proteomics technology for the first time,we screened the related differential proteins of PPT dropping pills against tachyarrhythmia and explored their potential mechanisms of action.The results showed that 44 differentially expressed proteins in tachyarrhythmia induced by barium chloride were selected,including 24 up-regulated proteins and 20down-regulated proteins.40 differentially expressed proteins in PPT dropping pills were anti tachyarrhythmia,including 14 up-regulated proteins and 26 down-regulated proteins;GO enrichment analysis showed that the differentially expressed proteins of PPT dropping pills against arrhythmia were mainly distributed on the cell membrane and involved in various metabolic processes.The main molecular functions involved binding,transcriptional regulation,enzyme activity,and other aspects.KEGG enrichment results showed that the mechanism of PPT dropping pills against arrhythmia might be through regulating lipid metabolism,vascular smooth muscle contraction,chemokine signaling pathway,PI3K Akt signaling pathway,diabetes cardiomyopathy and other pathways.Cyp20a1,Cd300lg,Efl1,Stk38,Vti1a,Ube2b,etc.are important targets.In summary,it is shown that PPT dropping pills can improve the clinical symptoms of rats with tachyarrhythmia and regulate relevant biochemical indicators.The results of metabolomics and proteomics show that PPT dropping pills can pass glycerol phospholipid metabolism,retinol metabolism,ether lipid metabolism,arachidonic acid metabolism,sphingolipids metabolism,intercellular junction,Th17cell differentiation,base excision repair pathway,vesicular transport,PI3K-Akt signal pathway,The biosynthesis of eukaryotic ribosomes,adipocyte factor signaling pathways,and other metabolic pathways regulate rat tachyarrhythmia at multiple targets.Based on the results of metabolomics and proteomics,it was found that lipid metabolism is the main metabolic pathway,suggesting that PPT dropping pills have biological activity against tachyarrhythmia,and its mechanism may be mainly related to antioxidant and lipid metabolism regulation.This paper provides important reference and theoretical basis for further developing PPT dropping pills as antiarrhythmic drugs.