| Alcoholic fatter liver disease(AFLD) is the early stage of alcoholic liver disease,and the majority can recover from illness after treatment. Alcoholic fatty liver diseases were likely to become cirrhosis after 10 or 15 years in the case of no good treatment as reported. Epidemiological survey found that long-term chronic alcohol stimulus has become the first cause of fatty liver disease.Hesperidin is a flavonone derivant by the formative glycoside of hesperetin and rhamnosidoglucose. Hesperidin is a very important element of the citrus pulp and peel, which is abundant and inexpensive.Its pharmacological activity has been concerned widely. Previous studies in our laboratory show that HDN has good therapeutic effects on liver injury and nonalcoholic fatty liver.The aim of the present study is to explore the therapeutical effects of HDN on AFLD and to analyze the possible mechanism of HDN effects in rats fed with intragastric alcohol of increasing concentration gradually and fat emulsion. The main contents are divided into some sections as follows:1.Protective Effect of HDN on alcoholic fatty liverThe rats of the model group were fed with alcohol and high fat diet. The rats of HDN group(80,160,320mg/kg) and tiopronin group (60mg/kg) were administrated with related dose of medidine for six weeks. All rats were sacrificed by the end of the 6th week. The histopathological analysis showed that HDN can significantly alleviate the symptoms in the hepatopathy rats including hepatic steatosis, lobular inflammatory cells infiltration and necrosis. HDN effectively reduced liver index and ALT,AST in the serum .These results suggested that HDN has positively protective effects on alcoholic fatty liver in rats fed with intragastric alcohol of increasing concentration gradually and fat emulsion.2.The effects of HDN on lipid metabolism of alcoholic fatty liverCompared with the normal control group, TC, TG levels of model group in serum increased significantly, which indicating that the rats in model group have lipid metabolism disorders induced by alcohol. HDN can effectively reduced TC, TG levels in serum, suggesting that the effects of HDN on alcoholic fatty liver might be associated with regulating lipid metabolism and reducing fat deposition.3.The effects of HDN on oxidization of alcoholic fatty liverCompared with the normal control group, MDA levels of model group in liver increased significantly and SOD activity of model group in liver decreased significantly which indicats that the model group loose the balance between oxidation and antioxidation caused by alcohol. With the increasing of oxygen free radicals, lipid peroxidation have initiated. HDN can effectively reduced MDA levels in liver, and increased SOD activity in liver, suggesting that the effects of HDN on alcoholic fatty liver might be associated with enhancing the ability of cleanning oxygen free radicals and reducing lipid peroxidation to protect liver cells from the damage4.The effects of HDN on inflammatory reation of alcoholic fatty liverCompared with the normal control group, TNF-αlevels of model group in liver increased significantly, suggesting the existence of inflammatory response. The levels of TNF-αin serum was remarkably reduced after giving HDN, suggesting that effects of HDN on alcoholic fatty liver might be associated with inhibiting the releasing of flammatory cytokines TNF-αand reducing the inflammatory response of liver cells to restore liver function.5.The mechanisms of HDN prevent alcoholic fatty liver in ratsCompared with the normal control group, the mRNA expression of PPAR-γwas obviously decreased in model group. RT-PCR analysis showed HDN(160,320mg/kg) significantly increase the mRNA expression of PPAR-γ. Compared with the model group, HDN(160,320mg/kg) effectively depressed abnormally high expression of TNF-αand NF-κBP65 mRNA in hepatic tissue. The results suggested that its pharmacological mechanism might be related with adapting blood lipid component and antioxidative activity,downrugulating the mRNA expression of NF-Κbp65 and TNF-αproduction,upregulating expression of PPAR-γ.
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