| Background Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common liver disease which has done harm to the health of human beings in the world. In its initial phases, liver cells only show up fatty degeneration. In advanced stages, fatty hepatitis, hepatic fibrosis and hepatic cirrhosis will occur. Many studies showed that insulin resistance (IR) and oxidant stress play the important roles in the pathogenesis of NAFLD. Improving IR and antioxidant have been the foucs on treatment of NAFLD recently. Studies showed insulin sensitizer-rosiglitazone and antioxidant- VitaminC (Vit C) that can improve blood fat (BF), blood glucose and hepatic steatosis. There were few studies about effects of rosiglitazone on intervening NASH and rosiglitazone connecting with Vit C on treatment of NAFLD.Objective1 Effects of rosiglitazone on prevention of NASH2 Effects of rosiglitazone on treatment of NASH3 Effects of rosiglitazone combining with Vit C on NASH.MethodsNormal male SD rats were randomly devided into 11 groups.There were 3 model groups with a high-fat diet (M1, M2, M3,n=6). There were 3 normal control groups with normal diet (N1, N2, N3, n=6). M1,N1 and M2,N2 were sacrificed respectively at week 12 and week 16.There were 5 therapy groups feded with high-fat diet. NASH prevention group (R1, n=8) was givern rosiglitazone at week 12 and was sacrificed at week 24. Low dose rosiglitazone group (R2, n=8),large dose rosiglitazone group (R3, n=6), Vit C group (C, n=8), and rosiglitazone combining with Vit C group (R+C, n=8) were all given drugs at week 16. Those rats and M3, N3 were sacrificed at week 24. Weight (W), liver wet weight (LWW), liver index (LI), viscera fat quality (VFQ), blood fat (BF), fasting blood glucose (FBG), fasting insulin (FIns), tumor necrosis factor (TNF-α), serum transaminase, urea, creatinine (Cr), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Observe the degree of liver steatosis, inflammation and fibrosis by HE stain and Masson stain. Observe oxidant stress in liver by 3-nitrotyrosine immunohistochemistry stain.Results1 W, LWW, LI, MDA and liver inflammation in R1 group were improved compared with that in M3 (P<0.05), and VFQ, SOD, TG, LDL, liver inflammation, liver fibrosis and liver oxidant stress were improved significantly (P<0.01). TNF-α, FBG, FIns and HOMA-IR decreased (P>0.05). And ALT, AST, UREA, Cr had no significant change.2 HOMA-IR, TG, liver inflammation, liver fibrosis and liver oxidant stess were improved significantly in all therapy groups. MDA (R2 and C vs M3, P<0.05;R+C vs M3,P<0.01),SOD and TNF-α(R2, R3 and R+C vs M3,P<0.01;C vs M3,P<0.05) were improved. TC(P<0.01), MDA(P<0.01), SOD(P<0.01) and liver fibrosis(P<0.05) in R+C group were better than R2. Liver fibrosis in R3 group was better than that in R2. ALT, AST, UREA, Cr had no significant change in all groups.Conclusions1 Rosiglitazone can improve systemic and local oxidant stress, BF, liver inflammation and liver fibrosis in preventing NASH.2 Rosiglitazone and combination therapy can improve systemic and local oxidant stress, IR, TG, LDL and decrease liver steatosis, liver inflammation, liver fibrosis. TC, MDA, SOD and liver fibrosis in combination therapy group were better than low dose rosiglitazone group.3 There is no significant difference between solo rosiglitazone and combination therapy on improving IR.4 There are significant differences on liver fibrosis in group R3 and R+C.5 Rosiglitazone has no effect on liver and renal function.
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