Abstract: To investigate the protective effect of Broussonetiae Fructus on acetaminophen-induced liver injury in rats and the regulatory effects on peroxisome proliferators activated receptor α (PPAR-α),peroxisome proliferators activated receptor γ (PPAR-γ),and C-Ros oncogene 1 (ROS1).50 SD rats were randomly divided into normal group,model group,silymarin group (44 mg/kg),Broussonetiae Fructus high and low dose groups (4.2，1.05 g crude drug/kg) with 10 rats in each group.The rat model of drug-induced liver injury was induced by acetaminophen (1.2 g/kg) orally once daily for 30 days.At the same time of modeling,normal group and model group were given saline infusions by gastric lavage,while the rest groups were given corresponding liquid infusions for 30 days.At the end of the experiment,the activities of AST,ALT,SOD,CAT and GSH-Px,and the contents of TBIL,DBIL,MDA and GSH in serum were measured.Part of the liver tissue was fixed with 4% paraformaldehyde solution,the pathological morphology of the liver was observed with HE staining,and the gene expression of PPAR-α and PPAR-γ were observed by RT-PCR,and the protein expression of ROS1 (C-Ros oncogene 1) was observed by immunohistochemistry.Our results showed that compared with the normal group,the levels of ALT,AST,TBIL and DBIL in rats of the model group were significantly increased,the content of MDA in serum and the gene expression of PPAR-γ in liver were increased,while the levels of SOD,GSH,GSH-Px and PPAR-α were decreased.Compared with the model group,different doses of Broussonetia Fructus could reduce the levels of ALT,AST,TBIL and DBIL,increase the levels of SOD,GSH,GSH-Px in serum,inhibit the gene expression of PPAR-γ and the protein expression of ROS1,and up-regulate the gene expression of PPAR-α.In conclusion,the results of this study suggest that Broussonetiae Fructus may have protective effect on the hepatic injury induced by acetaminophen in rats,and its mechanism may be related to the inhibition of oxidative stress and regulation the gene expression of PPAR-γ,PPAR-α,and the expression of ROS1 protein.

Key words: drug-induced liver injury, fructus broussonetia, ROS1, PPAR-&gamma, , PPAR-&alpha,