Effect Of Berberine (Ber) On Expression Of Peroxisome Proliferators Activated Receptors Alpha (PPARα) MRNA And Protein In Liver Tissue Of Non-alcoholic Fatty Liver Disease Rat

Objectives:To study the effects of berberine on PPARαmRNA and protein expression in the hepatic tissue of nonalcoholic fatty liver disease(NAFLD) in rats and to explore its molecular mechanism.Methods:66 male SD rats were randomly divided into two groups:high fat diet group(n=56, fed with high fat diet) and the normal group(n=10,fed with normal diet).12 weeks later,all rats fed with high fat diet were divided into 5 subgroups:high-dose berberine group,low-dose berberine group,Dongbaogantai group,model group and natural recovery group.8 weeks after treatment,the contents of serum TC,TG,LDL-C,ALT,AST,etc were assayed by automatic biochemistry analyzer and the histopathological change of hepatic tissue was observed by light microscope.The expression of PPARαmRNA was detected by RT-PCR, and the protein was measured by immunohistochemistry.Results:1.Compared with normal group,the contents of serum TC,TG,ALT,AST,LDL-C in the model group were significantly increased(P＜0.01).Compared with the model group,the contents of serum TC,TG,HDL-C,ALT and AST in each treatment group were decreased, while no significant difference was found between the treatment groups and natural recovery group(P＞0.05).But the above indications showed an improvement tendency in high-dose berberine treatment group.2.Light microscope observation revealed medium degrees of fatty degeneration in hepatocytes in model group:swelling of hepatocytes and different sizes of lipid droplets inside the cytoplasm.Inflammatory cells were seen in the hepatic lobules of model rats.No piecemeal necrosis,bridging necrosis and fibrosis were seen in the hepatic tissue of model control rats.In berberine groups,there shows mild fatty degeneration in hepatocytes but no obvious infiltration of inflammatory cells.In Dongbaogantai group and natural recovery group,there shows fatty degeneration from mild to medium degrees in hepatocytes and small amount of inflammatory cells.3.The expression of PPARαmRNA and protein in hepatic tissue of model group were significantly lower than that of normal group(P＜0.05).Compared with model group,the expression levels in all treatment groups were increased,but no significant difference was found between the treatment groups and natural recovery group(P＞0.05),but improvement tendency was found in high-dose berberine treatment groupConclusions.1.High fatty diet can successfully reproduce rat models of NAFLD.2.Diet control can reverse hepatic steatosis in the early metaphase of NAFLD3.Berberine combined with high fat diet control can prevent and control NAFLD probably through various mechanisms,such as adjusting lipid metabolism,ameliorating fatty degeneration of hepatocytes,protecting hepatocytes,ameliorating inflammation and improving liver function.4.Berberine combined with high fat diet control could up-regulate the expression of PPARαmRNA and protein in the hepatic tissue,which may be one of the mechanisms for preventing and controlling NAFLD.5.Berberine shows certain therapeutic effect on NAFLD,but no significant effect in the early stage.Therapeutic effect of berberine on NAFLD needs further research as the course prolonged and fatty degeneration aggravated.