Study On Effects Of Fenofibrate On Intestinal Microflora In Hyperlipidemia Golden Hamster And Its Correlation With Effects On Lowering Blood Lipid

As the "metabolic organ" of the body,intestinal flora is closely related to the metabolism of the body.Related studies have shown that the imbalance of intestinal flora is a contributing factor of metabolic diseases related to hyperlipidemia,and the intervention and treatment of microflora can significantly reduce blood lipids.Fenofibrate,as a first-line clinical lipid-lowering drug,has a significant effect on reducing blood lipids,but its lipid-lowering mechanism has not been fully explained.Intestinal microorganisms are the therapeutic targets of metabolic diseases,but it is unknown whether the lipid-lowering effect of fenofibrate is related to intestinal microflora.Aims:To explore the effect of fenofibrate on intestinal flora in hyperlipidemia golden hamsters and its relationship with its hypolipidemic effect,and to provide a new target of intestinal microecological intervention for the treatment of hyperlipidemia.Methods:1.Establishment of hyperlipidemic model in golden hamsters.Male golden hamsters were fed with D12108 C high-fat diet in the high-fat diet group and standard diet in the blank control group.The biochemical detection of blood lipids was carried out after 10 days of continuous feeding,including total cholesterol(Chol),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C)and triglyceride(TG),to judge the success of the model.2.Effects of fenofibrate on blood lipids and liver lesions in hyperlipidemic golden hamsters.The golden hamsters successfully modeled were divided into hyperlipidemia model group and fenofibrate intervention group(n = 6).Fenofibrate intervention group continued to receive high-fat diet and fenofibrate(50mg/kg),hyperlipidemia model group continued to receive high-fat diet and normal saline,the blank control group was given standard diet and normal saline,the administration volume in each groups all was 16.7 ml/kg,once per day for 4 weeks.After intervention,the hamsters were anesthetized with 3% pentobarbital sodium,and the contents of blood,liver and intestines were collected for detection.Biochemical detection,including serum Chol,LDL-C,HDL-C,TG,pyruvic transaminase(ALT)and glutamic oxaloacetic transaminase(AST),and histopathological examination of liver were conducted.3.Study on the relationship between the hypolipidemic effect of fenofibrate and intestinal flora.The collected intestinal contents were detected by 16 Sr RNA,the test results were analyzed,and the correlation between differential flora and blood lipids and liver enzymes was analyzed.Results:1.Ten days after the establishment of the model,the levels of Chol,LDL-C and HDL-C in the high-fat diet group increased significantly,and the TG increased with a obvious tendency,suggesting that the hyperlipidemia model in hamsters was established successfully.2.The results of biochemical and pathological tests showed that fenofibrate could significantly reduce the levels of Chol,TG and LDL-C in hyperlipidemic hamsters,and significantly improve the inflammation and steatosis of liver,and reduce the levels of ALT and AST.3.Based on 16 Sr RNA sequencing,in PCA,PCOA and NMDS analysis,we found for the first time that the intervention of fenofibrate could restore the intestinal flora structure of hyperlipidemic hamsters to the blank control group,and it was also verified again in UPGMA analysis.In this study,it was found for the first time that fenofibrate decreased the relative abundance of Firmicutes phylum and Proteobacteria phylum in hyperlipidemic hamsters and increased the relative abundance of Bacteroidetes phylum and Saccharomyia phylum in hyperlipidemic hamsters.After the intervention of fenofibrate,it was found that there were significant differences in the relative abundance of Bacteroidetes phylum,Proteobacteria phylum,Saccharibacteria phylum,Bacteroidia class,unidentified?Saccharibacteria class,Bacteroidales order,unidentified?Saccharibacteria order,Bacteroidales-S24-7-group family,unidentified?Saccharia family,Lachnospiraceae genus,Lachnospiraceae-NK4A136 genus,unidentified-Ruminococcaceae genus,[Eubacterium]-coprostanoligenes-group genus and Candidatus?Saccharimonas genus at the level of phylum,class,order,family and genus.And these differential bacteria were significantly correlated with the levels of blood lipids and liver enzymes.Conclusion:In this study,the hyperlipidemia model in golden hamsters was successfully established,and the improvement of blood lipid and liver function of hyperlipidemia hamsters treated with fenofibrate was further verified.Based on 16 Sr RNA analysis,it was found for the first time that the intervention of fenofibrate could significantly restore the intestinal flora of hyperlipidemic hamsters,and found that the difference of microflora was significantly related to the levels of blood lipids and liver enzymes,in which the recovery of Bacteroidetes phylum and Saccharibacteria phylum may be the key to the improvement of blood lipid levels.This study shows that the recovery of intestinal flora by fenofibrate plays an important role in the treatment of hyperlipidemia,which provides a scientific basis for intestinal microecological intervention in the treatment of hyperlipidemia.