LXR-α,SREBP-1c Expression In The Liver Of NAFLD Rat Model And The Intervention Study Of Rosiglitazone

Objective:To prepare rat model of non-alcoholic fatty liver disease by fat-rich diet.Rosiglitazone of low dose and high dose was given in different time to group L1,group H1,group L2 and group H2.At the end of twelve week,all the rats were sacrificed.TC,TG of serum and LXR-α,SREBP-1c expression of liver were measured to investigate the implications of LXR-α,SREBP-1c in the development of NAFLD, dependability between the hepatic pathological change and the variance were evaluated.And to investigate Rosiglitazone's protection effectiveness that in the development of NAFLD and the mechanisms.Methods:forty-two SD rats were randonmized into normal control group,NAFLD group,Rosiglitazone eraly intervention group (fed with fat-rich food,then after 4 weeks divided the group into 2 subgroups :low dose group and high dose group)and Rosiglitazone late intervention group(fed with fat-rich food,then after 8 weeks divided the group into 2 subgroups:low dose group and high dose group);By the end of 12thweek,all rats were killed to isolate the serum and the liver to test the level of weight,liver exponent,TG,TC,ALT and AST.The level of steatosis was observed under light microscope after haematoxylon-eosin (HE)staening.And then expression levels of LXR-α,SREBP-1c were assayed by immuno-histological chemistry. The experimental data between both groups was compared by two-sample average test.Results:1. Compared with control group,body weight and liver exponent were increased in model group(P<0.05);Body weight in Rosiglitazone-treated groups was higher than in model group,but liver exponent was obviously lower (P<0.05),and early intervertion group was lower than late intervention group in dose-dependent.2. Compared with control group,there was hyperlipidemia in model group (P<0.05),which was improved by Rosiglitazone (P<0.05),and early intervertion group was lower than late intervention group in dose-dependent.3. Compared with control group,there was hepaticsteatosis in model group(P<0.05),mostly in moderate or severe level;Rosiglitazone significantly attenuated the pathological changes in the liver (P<0.05),and early intervertion group was lower than late intervention group in dose-dependent.4. Compared with control group,the mRNA and protein content of LXR-α,SREBP-1c were obviously increased in model group(P<0.05),but were significantly decreased by Rosiglitazone(P<0.05),and early intervertion group was lower than late intervention group in dose-dependent.Conclusions:1. Non-alcoholic fatty liver disease animal model was sucessfully bulit by fed with fat-rich diet.2. LXR-αwas increased in steatosis model animals,and might be involved in non-alcoholic liver through up-regulating the expression of SREBP-1c.3. Rosiglitazone may decrese steatosis gradings through decreasing the expression of LXR-α;the therapeutic effect in early intervention group was better than in late intervention group,and was dependent on dose.