Effects Of Chinese Herbal Compound On Cytochrome P4502E1 And P4501A1 Expression In Rats With Nonalcoholic Steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) is increasingly considered to be the commonest liver disease in western countries. Amount of patients in our country is becoming more and more in recent years. It comprises a disease spectrum which includes variable degrees of simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Non-alcoholic steatohepatitis (NASH) is characterized by hepatocyte injury, inflammation and fibrosis which can lead to cirrhosis, liver failure [1]. Thus, it has important to prevent non-alcoholic steatohepatitis progress to liver fibrosis or cirrhosis.The pathogenesis of non-alcoholic fatty liver disease was not definite up to now. At present, it was considered to relate to factors as followed: lipid metabolism disturbance,insulin resistance,oxidative stress,lipid peroxidation and so on . Oxidative stress and lipid peroxidation is a key link in the formation of fibrosis [2].Recently, more and more research demonstrated the cytochromeP450 (CYP450) is closely correlated with non-alcoholic fatty liver disease. CytochromeP450 that might affect the liver lipid metabolism induced lipid peroxidation. Thus, the current research on early prevention and treatment of non-alcoholic steatohepatitis may be one of the hot spots [3-4].Objective:To study the mechanism of action and the effect of Chinese herbal compound (CHC) on cytochromeP4502E1 (CYP2E1) and cytochromeP4501A1 (CYP1A1) expression in rat with nonalcoholic steatohepatitis (NASH). Methods:Fifty-six SD rats were randomly divided into normal control group (C), low dose treatment group (LT), middle dose treatment group (MT), high dose treatment group (HT), positive control group (PC), model group (M) and prevention medicine group (P). Copy the model of NASH with a high fat diet. NASH rats were treated according to low dose, middle dose and high dose from 5th week. The rats were killed at the end of the 12th week. The malondialdehyde (MDA) and glutathione reductase (GR) in the blood serum were measured. The malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver were observed. The liver pathology changes were observed under light microscopy by HE staining and sudan III staining; Hepatic cytochromeP4502E1 (CYP2E1) and cytochromeP4501A1 (CYP1A1) were assayed with Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR).Results:At the end of 12th week ,compared with model group, the value of MDA decreased(P<0.05), GR increased(P<0.05) in middle dose treatment group. CHC could decrease the activity of MDA in liver and increase the activity of SOD (P<0.05). The degree of fat degeneration and inflammatory necrosis was ameliorated remarkably (P<0.05). The hepatic expression of CYP2E1 and CYP1A1 were down-regulated compared with those in model group (P<0.05).Conclusion: CHC could prevent the fatty liver of rats and the mechanism may be related to its effects on improving fat metabolism disorder, raising capability to pellate oxygen free radical of body, and inhibiting cytochromeP4502E1 and P4501A1 expression.