| Purpose:In this study,the model of Murine NAFLD were established with chr onic high-fat diet to investigate the changes of bile acid in NAFLD rats and how sulforaphane improve the NAFLD rats by regulating bile acid metabolism.Methods:Sixty male Wistar rats were fed for three days adaptively and divided randomly into six groups according to body weight including Control group,model group,medicine therapy group,SFN group[Divided into high dose group 20mg/kg,medium dose group 10 mg/kg and low dose group 5 mg/kg].The NA FLD model was established by chronic high-fat diet for 10 weeks and three times per week.The control group fed normal feed,the remaining groups fed high fat die t and all rats given free drinking water.While mice in control group was given sal ine and model group gavage with equal volume of salad oil,the SFN group was dis solved in SFN by salad oil and the medicine therapy group was given Yi Shan Fu(Yi Shan Fu,30mg/kg,dissolved by Salad oil).After the experiment.At the end of the study,all mice were killed.Blood and liver were collected for further deter minations.Serum lipids,cholesterol-alpha hydroxylase and HMG-COA were detecte d by enzyme-linked immunosorbent assay.Morphologic changes of liver were observ ed by optical and electronic microscope.RT-PCR was used to detect the gene expres sion of liver CYP7A1,HMG-COA,liver X receptor and farnesyl esterase receptor.Western blot was used to detect the protein expression of LXR and FXR in the liv er.Result:(1)General indexes:Compared with Con group,the HFD group showed asignifica nt increase in physiological parameters and serological markers(body weight,TG,TC,TBA,LDL-C)(P<0.01);Compared with HFD group,body weight and serological m arkers of SFN group decreased to some extent,while in H/M group were significa ntly decreased(P<0.01).(2)Pathological changes:Compared with the Con group,the HE staining of the liver of HFD group showed obvious infiltration of inflammatory cells and fat,while the SFN treatment groups reduced the infiltration of liver fat;(3)The content and expression level of CYP7A1,HMG-COA in liver:Compared with Con group,the level of CYP7A1 in liver of HFD group decreased significantl y(P<0.01),while the level of HMG-COA increased(P<0.01).However,the expres sion of CYP7A1 mRNA was significantly decreased(P<0.01),and the expression o f HMG-COA mRNA was significantly increased(P<0.01).Compared with HFD gro up(P<0.01),and the level of HMG-COA in SFN-treated rats decreased significantl y(P<0.01),while the levels of CYP7A1 mRNA(P<0.01).The expression of HMG-COA mRNA was significantly decreased.And the H group decreased significantly(P<0.01).(4)The expression of LXR and FXR in rat liver:Compared with Con group,the expression of FXR mRNA in HFD group was significantly increased(P<0.01),the expression of LXR mRNA was significantly decreased,the difference was significa nt(P<0.05).Compared with HFD group,the expression of FXRmRNA in liver decr eased significantly in SFN intervention group(P<0.01),and the expression of LXR mRNA in H group was significantly lower than that in HFD group Significant(P<0.01).Western blot is consistent with the gene expression level.Conclusion:1.SFN intervention can significantly reduce the body weight of non-alcoholic fatty 1 iver,which reduce TG,TC,LDL-C,serum TBA levels and improve NAFLD.2.SFN may increase the mRNA transcription and protein expression of CYP7A1,w hich was considered be due to both the enhancement of the mRNA transcription an d protein expression of LXR and the the inhibition of protein expression of FXR i n liver.3.SFN may also inhibit transcription of HMG-COA by increasing the mRNA transcription and protein expression of LXR. |
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