Effects Of Berberine Combined With Exercise In The Treatment Of Non-alcoholic Fatty Liver Disease In Rats With Metabolic Syndrome

ObjectivesNon-alcoholic fatty liver was the liver manifestation of metabolic syndrome,which was the target organ damage caused by the disorder of blood glucose and lipid metabolism.In order to better treat the disease,the stable and reliable model of metabolic syndrome was established by feeding rats with high-fat diet,and the therapeutic effect of non-alcoholic fatty liver of metabolic syndrome was observed by drug therapy and sports lifestyle intervention on the basis of the model.The extensive pharmacological mechanism based on berberine has gradually become a research hotspot in recent years.In this study,berberine was used to treat and/or exercise to intervene metabolic syndrome rats fed with high-fat diet,to explore the related mechanism of improving non-alcoholic fatty liver disease,and to provide reliable animal experimental basis for clinical treatment in the future.MethodsThis experiment adopted Otsuka Long-Evans Tokushima Fatty(OLETF)as the experimental animal model of rats,the rats by gene mutation after gallbladder contraction-1 receptor dysfunction,leading to feed more,obesity,insulin resistance,after feeding high-fat diet gradually for the development of type 2 diabetes,high blood pressure,high cholesterol,and associated with nonalcoholic Fatty liver disease,and taked the strains long-evans tokushima otsuka(LETO)to contrast group(L-SED)in rats,establishing stable OLETF rats model of the metabolic syndrome.On the basis of the metabolic syndrome model to continue by feeding high-fat diet rats,we divided into four groups and entile berberine group(O-BBR group),exercise group(O-Ex group),BBR and exercise group(O-B+Ex group),meditation group(O-SED group),after monitoring serum biochemical index,put to death animals associated with the liver HE staining,protein extract relevant organizations,through statistical analysis of each group related biochemical indexes,liver mitochondrial function protein,fatty acid metabolism related proteins were statistically difference,in order to explore related mechanisms that whether berberine and exercise could improve the metabolic syndrome in rats of non-alcoholic fatty liver.Results1.The body mass,fasting blood glucose,fasting insulin level,total cholesterol,triglyceride,systolic and diastolic blood pressure,and insulin resistance index of rats in the metabolic syndrome group were significantly higher than those in the control group after 20 weeks of high-fat feeding(26 weeks of age),suggesting that the metabolic syndrome model of OLETF rats fed with high fat was successfully constructed.2.O-SED group’s body quality,fasting glucose,fasting insulin level,total cholesterol,triglycerides,free fatty acids,cereal third transaminase,insulin resistance index were significantly higher than that of L-SED group(P<0.05),separate O-BBR,separate O-Ex group,the two joint after the above indexes were lower than that of O-SED group(P<0.05),and the two combined index is lower than single O-BBR group or single O-Ex group(P<0.05).3.HE staining results indicated that the liver tissue structure of L-SED rats was normal,and non-alcoholic fatty liver disease occurred in o-sed rats.The degree of hepatic steatosis was reduced in O-BBR group and O-EX group,and the degree of hepatic steatosis was further reduced in O-B+Ex group.4.Compared with the L-SED group,the PPARα protein and mRNA levels in the o-sed group were significantly decreased(P<0.05),and the PPARα protein and mRNA levels in the O-BBR group,the O-EX group,and the O-B+Ex group were significantly increased(P<0.05),and the PPAR protein and mRNA levels in the O-B +Ex group were significantly higher than those in the O-BBR group or the O-EX group(P<0.05).Compared with L-SED group,O-SED group PGC-1α protein and mRNA levels were significantly increased(P<0.05),O-BBR group PGC-1α protein and mRNA level after treatment compared with O-SED group were significantly lower(P<0.05),O-EX group of PGC-1α protein and mRNA level compared with O-SED group had no significant difference(P>0.05),O-B+EX group PGC-1α protein and mRNA level compared with O-SED group were significantly lower(P<0.05).Compared with the L-SED group,the levels of CPT-1α protein and mRNA in the O-SED group decreased significantly(P<0.05),and the levels of CPT-1α protein and mRNA in the O-BBR group,the O-EX group,and the O-B+EX group increased significantly(P<0.05),and the O-B+EX group was superior to the O-BBR group or the O-EX group(P<0.05).5.Compared with the L-SED group,the levels of CD36 protein and mRNA in the O-SED group increased significantly(all P<0.05),while the levels of CD36 protein and mRNA in the O-BBR group,O-EX group and O-B+EX group decreased significantly(all P<0.05),and the indicators in the O-B+EX group were lower than those in the O-BBR group or O-EX group(all P<0.05).Compared with the L-SED group,the levels of FAS protein and mRNA in the O-SED group increased significantly(P<0.05),while the levels of FAS protein and mRNA in the O-BBR group,the O-EX group and the O-B+EX group decreased significantly(P<0.05),and the indicators in the O-B+EX group were lower than those in the O-BBR group or the O-EX group(P<0.05).Compared with the L-SED group,the AMPK phosphorylation level in the O-SED group decreased significantly(P<0.05),and the AMPK phosphorylation level in the O-BBR group,the O-EX group,and the O-B+EX group increased significantly(P<0.05),and the O-B+EX group had better indicators than the O-BBR group or the O-EX group(P<0.05).Compared with the L-SED group,the ACC phosphorylation level of the O-SED group decreased,but there was no significant difference(P>0.05),and the ACC phosphorylation level of the O-BBR group,O-EX group,and O-B+ Ex group increased significantly(all P<0.05),and the O-B+ Ex group was superior to the O-BBR group or the O-EX group(P<0.05).Conclusions1.Berberine and(or)exercise could improve the body weight,insulin resistance,triglyceride,alanine aminotransferase and other related biochemical indexes of metabolic syndrome rats,and combination therapy was better than single therapy.2.Through the pathological observation by HE staining,berberine and(or)exercise could improve the non-alcoholic fatty liver of metabolic syndrome rats,and the degree of fatty liver degeneration could be further reduced by combined treatment.3.Berberine and(or)movement by enhancing function of mitochondrial protein(PPAα,CPT-1α)the expression of improve mitochondrial function,reduce fatty acid metabolism of protein expression(CD36,FAS)and improve the level of AMPK,ACC phosphorylation reduce fatty acid synthesis,thereby improving nonalcoholic fatty liver disease of metabolic syndrome rats,the combined treatment is better than that of single treatment.