| Fatty liver disease (FLD) includes alcoholic liver disease (ALD) by alcohol and non-alcoholic fatty liver disease (NAFLD) by hyperglycemia and obesity. At present, the most of patients with FLD can be caused by both of alcohol and high-fat diet in our country. High-fat diet could aggravate liver damage of ALD or not, what is the mechanism? What is the significance of cell apoptosis in the pathologic mechanism of FLD? Which way was involved in the inflammatory reaction in the liver of FLD induced by alcohol and high-fat diet? All those questions are not clear. Peroxisome proliferator-activated receptor-gamma (PPARγ) is one member of the nuclear hormone receptor superfamily that can be activated by various ligands. Recent studies showed that this transcription factor associated not only with adipocyte differentiation, insulin resistance, sugar and lipid metabolism; and also with the regulation of inflammation, hepatocyte proliferation and the apoptosis in human liver cancer cells. The role and the mechanism of PPARγin FLD has not been well addressed . It is important for the study of FLD to develop an animal model by a simple, convenient and practical method. The model is used to study the significance of cell apoptosis in liver of rats with FLD; to explore the molecular pathogenesis of FLD by observing the change of NF-κB binding activity, the expression of PPARγ protein and mRNA, and their relationship; to investigate the therapeutic affection of Fuganjiedu Chinese herbal compound on liver lesion in rats with ALD, to delineate the molecular mechanism of Chinese herbal treating ALD, and to provide rational data for using Chinese herbal treating patients with ALD.Methods and Results Preparation of FLD rat model and the change of serum TNFα, MDA of liver homogenate In order to look for a simple, practical method to establish rat model of FLD by alcohol and fat-rich diet; to study the relationship between the level of serum TNFα, the content of liver MDA and histology finding in the point of view of oxidative stress; and to establish the basis for studying the pathogenesis of FLD. Sixty Wistar rats were divided into four groups of ten each (except alcohol group 30 rats) randomly: normal control, alcohol group, fat-rich diet group, alcohol and fat-rich diet group. FLD rats model was made by feeding alcohol of increasing concentration gradually (40%-50%-60 %, 15kg -1 .L -1. d -1) intragastrically or high fat diet or both on the basis of standard diet. Ten rats from each group were sacrificed at the end of the 16th week from the feeding day. Serum and liver homogenate was isolated and stored in -200C refrigerator. Serum TC, TG, ALT, FFA and TNFα were measured using an Olympus AU 2700 auto –biochemical analyzer, colorimetric method and radio-immune assay (Beijing Furui) respectively. MDA in liver homogenate was detected using TBA kit (Nanjing Jiancheng). Some of livers were fixed in 10% buffered formalin and stained with hematoxylin-eosin for routine examination and with SudanⅣ for steatosis or with Masson for fibrosis. The ultrastructure of the livers was observed by HITACHI H7500 transmission electron microscope (TEM) after the samples underwent 4% glutaraldehyde-osmic acid fixation. The steatosis, inflammation, necrosis and slight fibrosis were presented in the liver of rats in different experimental groups at the end of 16th, in which steatosis was severe in alcohol and fat-rich diet group, fat-rich diet group, but inflammation and fibrosis was the worst in alcohol and fat-rich diet group. The quantitative evaluation of steatosis in rats of normal group, alcohol group, fat-rich diet group, alcohol and fat-rich diet group were 1.34±0.33, 12.79±2.73, 35.82±8.52, 37.97± 11.48 respectively; scores of inflammation were: 0.67±0.66, 4.35±0.56, 3.05±0.72, 5.71±1.03 respectively; that of fibrosis were 2.03±0.87, 11.85±3.89, 7.90±2.79, 19.02±4.01 respectively. TC, TG, ALT, TNFα, FFA in serum and MDA in liver homogenate were elevated significantly than that of normal control. The level of s...
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