Hyperlipidemia Effect And Mechanisms Of Total Stilbene From Cajanus Cajan L. In Hyperlipidemic Hamster

Applicating high fat diet induced method to establish hyperlipidemia hamsters model,using biochemical and molecular biology techniques to study cholesterol metabolism biomarkers of hyperlipidemia hamsters,and to evaluate the effect of sECC on serum lipid and hepatic lipid and discuss the mechanism of sECC on lipid-lowering in this paper.Syrian Hamsters were randomly divided into control group,model one group and model two group.The control group were fed normal diet,model one group fed with high fat diet recipe one(0.2%cholesterol,15%lard),and model two group fed with high-fat diet recipe two(0.1%cholesterol,10%lard).Drawn blood from orbital venous plexus during 1,2,3,4 weeks and serum lipids were measured.At the end of the experiment,blood and liver were taken,the serum lipids and hepatic lipid were measured.Using real-time quantitative PCR to assay the changes of relative mRNA expression of LDL-R,SREBP-2,CYP7A1,LXRa,FXR,CYP27A1.After established hyperlipidemia of hamsters,and then the animals were randomly divided into model group,positive drug simvastatin(12mg/kg),sECC high(400mg/kg),medium(200mg/kg),low(100mg/kg)dose group and normal control group according to blood lipid.Continuous gavage administration group for 3 weeks,drawn blood from orbital venous,serum lipids and hepatic lipid content were measures by enzyme assay.Real-time PCR and Western blot detect the dynamic changes of the key enzymes,proteins,receptors,cytokines in hepatic cholesterol metabolism.The experimental results showed that,the model one group and model two group were induced by high fat diet for 1 week,compared with the control group,the serum level of TC,TG and LDL-C were significantly increased.With prolonged modeling,model one group lipids remained at a high level and the stability were better than model two group.High fat diet recipe one could induce better hyperlipidemia of hamster.The mechanism research showed that hamsters induced by high fat diet,hepatic SREBP-2 mRNA expression reduced,thereby inhibiting the expression of LDL-R,LDL-C degradation by LDL-R pathway was blocked,causing increased blood LDL-C concentration.At the same time,hepatic FXR mRNA expression upregulate and LXR a mRNA expression downregulate inhibited the expression of CYP7A1 mRNA,and then cholesterol into bile acids were reduced,resulting in increased the level of TC.The lipid-lowering effect of sECC administration for 3 weeks showed that,compared with the model group,400mg/kg of sECC could reduce the serum TC and LDL-C by 27.3%(P<0.001)and 31.6%(P<0.01),200mg/kg of sECC could reduce the serum TC and LDL-C by 22.7%(P<0.001)and 22.I%(P<0.01),but there was no significant effect on TG concentration.Mean while sECC high doses could reduced the hepatic TC and TG by 71%and 56%(P<0.001),sECC medium dose group were 56%and 53%(P<0.001),and sECC low dose group were 41%and 30%(P<0.01).The mechanism research showed that,sECC group were compared with model group,the expression of HNF-1 a mRNA and protein were decresed and then down-regulate the expression of FXR mRNA and protein,thereby induced CYP7A1 mRNA expression and enzyme activity increased,the classical pathway of cholesterol into bile acid was activated.Finally accelerated liver cholesterol excreted.At the same time the expression of liver p38 mRNA and phospho-p38 MAPK protein were down regulated,and up-regulated the expression of hepatic LDL-R mRNA and protein,increasing the absorption of the liver on LDL-C and decreaing the serum LDL-C levelTo sum up,hamster induced by the high fat diet for one week could be formed hyperlipemia.This model's advantages were short of molding cycle,stable performance,hyperlipidemia features obvious.The changes of heptic SREBP-2,LDL-R,FXR,LXR a,CYP7A1 is main molecular mechanism of the disturbance of cholesterol metabolism in hyperlipemia hamster.The sECC administration for 3 weeks,could effectively reduce the levels of serum TC and LDL-C,and significantly reduce the concentration of liver TC and TG CYP7A1,FXR,HNF-1?,LDL-R,p38 MAPK were the main targets of lipid-lowering effect of sECC.