Effect Of Aspirin Eugenol Ester On Cholesterol And Bile Acid Metabolism In Hyperlipidemia Rats

With the continuous development of the pet industry,hyperlipidemia has become a high incidence of cardiovascular disease in companion animals such as dogs and cats.Related studies have shown that Aspirin eugenol ester(AEE)has a significant therapeutic effect on hyperlipidemia.In this study,the effects of AEE on the types and contents of bile acids in the liver of hyperlipidemia rats were studied to further explore the effects of AEE on the contents and regular changes of different bile acids in the liver.The main mechanism of AEE in the treatment of hyperlipidemia was investigated by detecting the influence of AEE on the changes of m RNA expression of genes related to cholesterol and bile acid metabolism in liver and small intestine.1.The experimental rats were divided into a blank group and a model group.The blank group was given maintenance diet,and the model group was given high-fat diet.Free feeding for 8 weeks in rats,the samples of blood,feces and liver were collected for test of serum blood lipid,total fecal bile acid determination,and liver general and microscopic pathological changes were observed.The results showed that all the indexes in the model group showed that the model of hyperlipidemia in rats was successfully established,which could be further studied.2.The rats in the blank group and the model group were divided into 8 groups: the blank group,the blank AEE group,the model group,the model AEE group,the model aspirin group,the model eugenol group,the model aspirin and eugenol(1 : 1)group,and the model atorvastatin group.After 5 weeks of intragastric administration,samples of blood,feces,liver and small intestine were collected,and the serum blood lipid level,fecal total bile acid content,hepatic eye view and microscopic pathological changes were observed and liver index was calculated.The results showed that after AEE intervention,all indexes of rats in the model group were significantly improved,indicating that the effect of AEE on hyperlipidemia rats was obvious,and other groups also had certain therapeutic effects on hyperlipidemia.3.Through absolute quantitative analysis of various bile acids in liver by LC-MS/MS,the results showed that compared with the blank group,the G-type bile acids were up-regulated and T-type bile acids were down-regulated in the model group.The changes of liver bile acid pool after each drug treatment were as follows: after AEE treatment,G-type conjugated bile acids was up-regulated,while T-type conjugated bile acids was down-regulated.After aspirin treatment,T-type combined bile acids was up-regulated and G-type combined bile acids was down-regulated.The liver bile acid pool of eugenol group did not change significantly.After aspirin-eugenol(1 : 1)treatment,the G-type bile acids was up-regulated.After atorvastatin treatment,T-conjugated bile acids were up-regulated.The result showed that after long-term high-fat diet induction,hyperlipidemia occurred in rats,while the diversity and content of bile acid pool in liver changed.The contents and types of bile acids of different types in liver changed regularly after each drug intervention.4.The effect of AEE on the mRNA expression levels of various genes related to the regulation of cholesterol and bile acid in liver and small intestine was studied by quantitative PCR.The resultsshowed that AEE down-regulated the expression of SREBP1 and up-regulated the expression of ABCA1 in the liver.Up-regulated the expression of CYP7A1 and CYP8B1 in the liver and down-regulated the expression of FXR in the liver and small intestine.The expression levels of NTCP,OATP1 and BSEP in the liver were down-regulated.Down-regulation of MRP2 expression in the liver.The results showed that the regulatory mechanism of AEE on cholesterol and bile acid metabolism in hyperlipidemia rats was mainly to promote the transformation of cholesterol in the liver into bile acid,and the excess bile acid was excreted in the feces.In summary,AEE has an obvious effect on the treatment of hyperlipidemia,and its therapeutic effect is related to the up-regulation of G-conjugated bile acids and the down-regulation of T-conjugated bile acid in the liver.AEE mainly down-regulated the mRNA expression levels of SREBP1 c,FXR,NTCP,OATP1,BSEP and up-regulated the mRNA expression levels of ABCA1,CYP7A1 and CYP8B1 to promote the transformation of cholesterol in the liver into bile acid and reduce the cholesterol content in the body and the amount of bile acid circulating in the liver.