ABSTRACT
AIM:To investigate the inhibitory effect of sinapine thiocyanate(ST)on hyperglycemia,hyper-lipemia,atherosclerosis and hepatocellular steatosis of ApoE-/-mice with insulin resistance(IR)and the possible mecha-nisms.METHODS:ApoE-/-male mice(n=60)were assigned randomly into control group ,saline group,rosiglitazone group and ST treatment groups(at low,middle and high doses )with 10 mice in each group.The mice in control group were fed with fundamental diet ,while the mice in other groups were fed with high-fat diet for 12 weeks.The mice in ST groups were given gavage with different doses of ST(10,30 and 90 mg· kg-1· d-1)simultaneously,while the mice in rosiglitazone group received gavage with rosigltazone(1.33 mg· kg-1 · d-1 ).In the last 3 weeks,the mice in control group received daily intrape-ritoneal injection of physiological saline ,and IR was induced in other groups by daily intrape-ritoneal injection of dexamethasone(0.8 mg/kg).The blood sample was collected and fasting plasma glucose was tested weekly through tail vein.After all animals fasted for 12 h at the end of the 12th week,they were sacrificed and the levels of fasting insulin,tumor necrosis factor-α(TNF-α),triglyceride,total cholesterol and liver lipids were measured.The li-ver tissue and aortic immobilized sections were detected by HE staining.The expression of the proteins related to liver lipid metabolism and skeletal muscle MAPK signaling pathway was determined by Western blot.RESULTS:ST showed dose-dependently reduced serum lipids ,plasma glucose and TNF-α(P<0.05),delayed hepatocellular steatosis and atheroscle-rosis,and dose-dependently regulated hepatic lipid metabolism signaling molecules(HMGR and SREBP-2)and MAPK signaling molecules(ERK and p38)(P<0.05).CONCLUSION:ST has the biological potential of reducing blood li-pids and relieving IR.The mechanism may be related to the regulation of liver lipid metabolism and skeletal muscle MAPK signaling pathway.