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The Effect Of Rosiglitazone On The Express Ion Of Peroxisome Proliferator-Activated Receptor Gamma(PPAR?) In Fatty Liver Of T Ree Shew

Posted on:2012-02-26Degree:MasterType:Thesis
Country:ChinaCandidate:X F GuoFull Text:PDF
GTID:2334330488956319Subject:Endocrinology
Abstract/Summary:PDF Full Text Request
Objective:To investigate the effect of rosiglitazone on the expression of peroxisome proliferator-activated receptor gamma (PPARy) in the liver of tree shrews with nonalcoholic fatty liver disease (NAFLD).Methods:Thirty tree shrews were divided into 2 groups:the chow di et group (group A, n=6) or the high sugar and high fat diet group (n=24) . After 22 weeks, out of those animals fed with high sugar and high fat diet 16 animals which had an increased FBG level equal to or more than 11.1 mmol/L were divided into 2 subgroups:no-intervention group (grou p B, n=9), rosiglitazone treatment group (group C, n=7), to which rosiglit azone was added at a dose of 5 mgkg-1·d-1 for 7 weeks. Body weight, fa sting glucose(FBG), fasting serum insulin(FINS), homeostasis model assess ment insulin resistance(HOMA-IR), blood lipids including total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were determined. Liver biops ies were collected under general anaesthesia at the end of the experiment in all animals for observing pathomorphology changes by optical microsc opy. The expression of PPARy in livers was detected by immunohistoch emistry.Results:Before our experiment, all parameters were comparable amon g the three groups. At the end of 22 weeks, FBG in group B or group C was significantly higher than group A, while it was comparable betwee n group B and group C. At the end of 29 weeks, The FBG, FINS and HOMA-IR of the group B was significantly higher than group A(P<0.01, P<0.05 and P<0.01 respectively), while group C was significantly lower than B(all P<0.01). The TC (P<0.01) and TG (P<0.05) in group C was s ignificantly lower than group B at 29th weeks. Morphological alteration u nder light microscope showed that all animals from group B had a typica 1 steatosis throughout the liver sections, while those in group C reduced markedly. The expression levels of PPAR-gamma in livers of group B we re up-regulated significantly compared with those of group A (p<0.01). In group C, the expression levels of PPAR-gamma were down-regulated sig nificantly compared with group B (P<0.05).Conclusion:Increased expression levels of PPARgamma in the liver may play an important role in the development of hepatosteatosis in tree shrews with high sugar and high fat diet. Rosiglitazone could improve ins ulin resistance in peripheral tissues and reduce (PPAR)-gamma expression in the liver and Maybe it is the mechnism by which Rosiglitazone impro ves hepatocyte steatosis.
Keywords/Search Tags:nonalcoholic fatty liver disease, rosiglitazone, insulin resi stance, peroxisome proliferator-activated receptor gamma, tree shrew
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