| Objective: NAFLD is a clinical syndrome, and has a spectrum ranging from that of fatty liver alone to nonalcoholic steatohepatitis (NASH), which may progress to liver cirrhosis and can progress to liver cell necrosis, fibrosis and cirrhosis of the liver. However the mechanisms underlying NAFLD are not well understood, and there is no effective preventative and therapeutic tool.Although several mechanisms like insulin resistance and oxidative stress are likely to contribute to this association , increasing attention has been directed to the role played by adipokines. In this study, we established rat NAFLD model by high-fat and high-cholesterol diet to try to explore the following vievpoint: (1)To observe the expression of peroxisome proliferator-activated receptorγmRNA in liver of rats in every stage of NAFLD model. (2)To investigate if traditional Chinese medicine----Jiangzhi Yigan Chongji can treat and prevent NAFLD through regulating the expression of peroxisome proliferator-activated receptorγmRNA. This investigation may provide new clues for the pathogenesis of NAFLD and instruct clinical medication.Methods: 70 male Wistar rats were randomly divided into 3 groups after fed with normal diet for 7 days. Normal control group(N group)were fed standard diet.Model control group (M group)were fed with high-fat and high-cholesterol diet which consisting of the standard diet, 13% lard and 2% cholesterol. Administration group (D group) were given Jiangzhi Yigan Chongji by intragastric administration while fed with high fat and high-cholesterol diet.Meanwhile each of the former three groups were divided into 3 subgroups (4,8 and 12weeks) respectively. Each subgroup has 10 rats. Administration group was given Jiangzhi Yigan Chongji (1ml/100g rat body weight, its concentration is 0.8g/ ml, twice every day) by intragastric administration separately after the end of 8th week, meanwhile, the normal and model group were separately given life drinking water by the same means. All the rats were sacrificed after 4,8 or 12 weeks. The following parameters were observed dynamically in each group: the level of aminotransferase and blood fat were detected by using automatic biochemistry analyzer; fasting blood glucose was detected by glucose oxidase method; serum free fatty acid was detected by copper staining method; serum insulin was detected by radio-immunity assay,simultaneously the insulin sensitivity index was calculated; the pathology of liver were observed by hematoxylin and eosin (HE) stain with microscopy; The expression of peroxisome proliferator-activated receptorγmRNA in rat nonalcoholic fatty liver model induced by high fat diet were assayed with reverse transcriptase-polymerase chain reaction (RT-PCR). Results:In control group, the liver lobules were distinct, the liver cell cords arranged regularly, every biochemical manifestation was all in normal range, the expression of peroxisome proliferator-activated receptorγmRNA was detectable in liver tissue.At the end of 4th week, the model group developed lipid metabolism disorder accompanied with hyperinsulinemia and insulin resistance, increase of aminotransferase, and the liver showed steatosis accompanied , the expression of peroxisome proliferator-activated receptorγmRNA in liver was lower than the model group.At the end of 8th week, the model group shew to be abdomen-form obesity,developed lipid metabolism disorder accompanied with hyperinsulinemia and insulin resistance, increase of aminotransferase, and the liver showed typical steatosis accompanied , the expression of peroxisome proliferator-activated receptorγmRNA in liver was significantly lower than the model group.At the end of 12th week, Compared with normal group, the level of aminotransferase and blood fat were increased in model group, at the same time, the levels of glutathione, high density lipoprotein cholesterol in serum was obviously reduced, the expression of peroxisome proliferator-activated receptorγmRNA in liver was more lower than the prophase group (P<0.01). Hepatocyte steatosis developed and liver presented the pathology of inflammation cell infiltration and sporadic punctiform necrosis, the inflammation score in model group were increased significantly compared with normal group (P<0.01).In the treated group, every biochemical manifestation shew improvement significantly, the expression of peroxisome proliferator-activated receptorγmRNA in liver was increased; steatosis and inflammation of liver show significant improvement ,too.Conclusion:1.The rats NAFLD model could be successfully established with the fed with high-fat and high-cholesterol diet . Insulin resistance, oxidative stress\lipid peroxidation damage were well associated with the development of NAFLD.2.The expression of peroxisome proliferator-activated receptorγmRNA in normal rats liver tissue was detectable. In NAFLD model group, it was significantly decreased at the end of 8th week and decreased significantly with the time.3.Jiangzhi Yigan Chongji was efective in the treatment and preventment of rats with NAFLD. Its molecular mechanism may be partly through up-regulating the expression of peroxisome proliferator-activated receptorγmRNA of the liver.
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