| Objective: 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 Cyclooxygenase mRNA in liver of rats in every stage of NAFLD model and to assess the relationship between intrahepatic Cyclooxygenase and NAFLD.(2)To investigate if traditional Chinese medicine----Jiangzhi Yigan Chongji can treat and prevent NAFLD through regulating the expression of Cyclooxygenase mRNA.This investigation may provide new clues for the pathogenesis of NAFLD and instruct clinical medication.Methods: 48 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 2 subgroups(8 and 12 weeks) respectively. Each subgroup has 8 rats.Administration group1,2 were given Jiangzhi Yigan Chongji (1ml/100g rat body weight, its concentration is 0.8g/ ml,twice every day)by intragastric administration separately after the beginning of the study,the end of 8th week and 12th week, meanwhile,the normal and model group were separately given life drinking water by the same means. All the rats were sacrificed after 8 or 12 weeks.The following parameters were observed dynamically in each group:Body weight was detected ; the level of aminotransferase,blood fat and lipid in liver tissue were detected by using automatic biochemistry analyzer; serum and liver free fatty acid were detected by copper staining method; reduced glutathione hormone (GSH), superoxide dismutase (SOD) activity and malondialdehyde (MDA) in serum and liver tissue were measured separately by using colourimetry, xanthinoxidase and thio-barbituric acid;the pathology of liver were observed by hematoxylin and eosin (HE) stain with microscopy; The expression of cyclooxygenase2 mRNA 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 cyclooxygenase2 mRNA was not detectable in liver tissue.At the end of 8th week, the model group shew to be abdomen-form obesity,developed lipid metabolism disorder, increase of aminotransferase,malondialdehyde in serum and liver and decrrease of the vitality of superoxide dismutase,the liver showed typical steatosis accompanied , the expression of cyclooxygenase2 mRNA in liver was significantly higher than the model group, the treated group shew improvement of every data, the expression of cyclooxygenase2 mRNA in liver was decreased ,and with statistical difference.At the end of 12th week,Compared with normal group,the level of aminotransferase ,blood fat and liver lipid content were increased in model group,at the same time,the content of malondialdehyde was increased,the levels of glutathione, superoxide dismutase, high density lipoprotein cholesterol in serum and liver were obviously reduced,the expression of cyclooxygenase2 mRNA in liver was more higher 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 cyclooxygenase2 mRNA in liver was decreased; 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 . oxidative stress\lipid peroxidation damage were well associated with the development of NAFLD.2. The expression of cyclooxygenase2 mRNA in normal rats liver tissue was not detectable. In NAFLD model group,it was significantly increased at the end of 8th week and increased significantly with the time.3. JYC was efective in the treatment and preventment of rats with NAFLD.Its molecular mechanism may be partly through downregulating the expression of cyclooxygenase2 mRNA of the liver.
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