The Effect Of Berberine On The Structure Of Intestinal Flora And Atherosclerosis In ApoE Receptor Gene Knockout Mice

BACKGROUND: Berberine has long been used in the treatment of bacterial diarrhea because of its antimicrobial activity.A large number of studies have shown that berberine has a potential role in the treatment of obesity,diabetes,hyperlipidemia and atherosclerosis.However,the bioavailability of berberine is low,and the mechanism of its treatment of metabolic disorders is not clear.The aim of this study was to investigate the role of BBR-induced gut microbiota modulation in the development of atherosclerosis?METHODS: Male ApoE-/-mice were fed with normal chow diet as control group(NC group),and atherosclerosis models were induced by high fat diet(HFD).Because of the coprophagic of mice,intestinal microorganisms can be transferred to each other through feces,we set up a group of mice fed with berberine and nonberberine high-fat diet in the same cage(CH group).At the end of the experiment,the levels of serum lipids in the four groups were examined;the difference of atherosclerosis,collagen and lipids of aortic sinus were observed by HE staining,oil red O staining and Masson staining in the frozen sections;the expressions of MMP-2,IL-6 and ICAM-1 of aortic sinus were observed by immunohistochemistry in paraffin sections;the m RNA transcription in carotid artery of TNF-a,MCP-1,IL-1?and VCAM-1 were tested by RT-PCR.Serum TMAO level was detected by mass spectrometry,Western blot was used to detect the expression of FMO3 in hepar.Fecal DNA was detected by denaturing gradient gel electrophoresis(DGGE),the gut microbiota structure was analysed by Quantity One software.We performed TA cloned of dominant bands and strain identified by sequencing.Results: The level of serum lipids in mice fed with high-fat diet for 12 weeks was significantly higher than that fed with normal chow diet,the area of atherosclerosis in aortic sinus was notable than that fed with normal chow diet.In addition,co-housing BBR-treated HFD mice with non-BBR-treated HFD mice reduced the development of atherosclerosis and the expression of inflammatory cytokines.Denaturing gradient gelelectrophoresis and principal component analysis showed that the gut microbiota of BBR treated HFD fed mice was significantly different from that of HFD fed mice,but similar to that of cohousing mice.In addition,BBR reduced the expression of FMO3 in liver and also serum TMAO level.Conclusion: The antiatherosclerotic effect of BBR is related to alterations in gut microbiota compositions,indicating the potential therapeutic value of pharmacological approaches that may modulate the gut microbiota in treating atherosclerosis.