Effects And Omics-based Mechanism Of Aspirin Eugenol Ester On Intervention Of Atherosclerosis And Prevention Of Thrombosis

With the application of gold hamster atherosclerosis(AS)model and metabolomic approach,the experiment was carried out to evaluate the intervention effects of AEE on AS.Combined with proteomic technology,the experiment was also performed to explore the potential mechanism of aspirin eugenol ester(AEE)in the prevention of thrombosis in carrageenan-induced rat tail thrombosis model,and find the difference of action way among AEE,eugenol(Eug)and acetyl salicylic acid(ASA).1.In hamster AS model,the aortic arch had typical AS pathological changes,accompanied by liver pathological damages and disturbance in biochemical indices.AEE could not only significantly improve the pathological injuries in liver cell,normalize blood lipid disorder,but also reduce the number of foam cells,inhibit the thickening of vascular wall,and ameliorate vascular stenosis.These results indicated that AEE had improving effects on AS.2.Metabonomic analysis results of plasma and urine from golden hamster showed that there was a significant different in metabonomic profile among control,model and AEE groups.AEE had a good regulation effect on metabolites in plasma and urine,and the anti-atherosclerosis effects of AEE might be related with amino acid metabolism,energy metabolism,pantothenic acid and CoA metabolism,riboflavin metabolism,glycerol phospholipid metabolism,et al.3.Metabonomic analysis results indicated that the metabolic profiles of liver and feces from golden hamster in control,model and AEE groups were obvious different.Twenty-eight differential metabolites were selected in liver and feces,and AEE could reverse the effect of high fat diet on partial metabolites.Metabolic pathway analysis showed that these metabolites were mainly involved in amino acid metabolism,glutathione metabolism,energy metabolism,glycerophospholipid metabolism,et al.AEE might play an important role in anti-atherosclerosis by regulating these metabolic pathways.4.In rat thrombosis model,results of plasma proteomics indicated that carrageenan could significantly affect the composition and expression of proteins associated with blood coagulation and platelet activation,and induce energy metabolism disorders and systemic inflammation.AEE mainly improved energy metabolism damage to inhibit thrombosis by the regulation of protein expression related with TCA circulation.ASA could down-regulate glutamate dehydrogenase,which had positive effects in energy metabolism and hepatocyte protection.Eug mainly inhibited the expression of proteins related with fibrinogen and blood coagulation regulation,then inhibiting the activation of platelets and coagulation factors.Results of parallel reaction monitoring(PRM)indicated that AEE,ASA and Eug had regulation effects on selected plasma proteins.However,there were differences in the regulation intensity of AEE,ASA and Eug.5.In rat thrombosis model,results of liver proteomics indicated that that carrageenan might induce thrombosis by affecting complement and coagulation cascade,oxidative stress,fatty acid metabolism,calcium channel regulation,arachidonic acid metabolism,et al.AEE could significantly reduce the expression of liver proteins related with complement and coagulation cascade,inhibit platelet activation and regulate HIF-1,MAPK and other signal pathways.The effect of ASA on liver protein was to affect the expression of proteins related with hemoglobin complex,cholesterol metabolism and the FoXo signaling pathway.Eug significantly regulated the liver proteins related with complement and coagulation cascade and hypoxia stress,and also had regulating effect on calcium channel and amino acid metabolism.PRM results were further confirmed the regulation effects of AEE,ASA and Eug on selected liver proteins,and also indicated the difference in the regulation intensity and action mechanism of AEE,ASA and Eug on liver protein.