| Background:The prevalence rate of fatty liver disease(FLD) is increasing today, and it's prevention and therapy also receive more attention. The mechanism of FLD is complex, however, there isn't uniform theory. Cytochr0me P450 2El (CYP2E1) is one of metabolic enzyme of microsom ethanol oxidation system(MEOS), and does an important role in exogenous and nitrogenous material metabolism. It has been known that the expression of CYP2E1 is increasing in FLD, and it consistent with steatosis hepatic cells' extent and distribution, which indicates CYP2E1 participates in the formation of FLD. When the disease progresses to steatohepatitis and steatofibrosis,the status of CYP2El'expression and correlated mechanism's researches haven't been reported until now.Objective:To sudy: (1) to study the effect of both alcohol and high fat diet and single on CYP 2El. (2) to study the relationship of CYP 2El and steatosis, inflammation, and fibrosis in fatty liver tissue,and discuss it's possible mechanism.Methods:46 male Wister rats were randomly divided into four groups according to their weights: alcohol group(A), high fat diet group(F), high fat diet and alcohol group(FA) and control group(N).30%-50% alcohol(v/v) by perfusion stomach, and it's content was increased gradually, 10mg/kg, bid. Rats in F group fed high fat diet,which comprised 2% cholesterol, 10% lard, and 88% normal diet. Rats in FA group were given both alcohol perfusion stomach and high fat diet. One rat was sacrificed randomly from each model group after 12 and 16 weeks, and histology examination was identified the formation of fatty liver and steatohepatitis. All rats were sacrified by femoral artery bleeding, and the following was measured: body weight, liver index(liver body and weight ratio); alanine aminotransferase(ALT), aspartate ??ainotranferase(AST), free fatty acid(FFA), triglycerides(TG), total cholesterol(TCH) in serum; HE dye, superoxide dismutase(SOD), malondialdehyde(MDA), glutathione (GSH), in hepatic tissue; CYP 2El in hepatic speciments by immunohistochemistry and CYP 2ElmRNA by RT-PCR. We make correlation analysis between CYP 2El and steatosis, inflammation, fibrosis, MDA in experiment group, and made analysis of variance(ANOVA), multiple comparisons and factorial design among groups.Results:1. ratsweight and liver index:Mean weight in F group was significantly higher than other groups(P＜0.05);compared with normal control group, liver index of the model groups was significantly higher(P＜0.05). It was highest in FA group, then F and A.2. hepatic histologic findings:The model groups had remarkable fatty liver, steatohepatitis. The level of steatosis and steatohepatitis was significantly higher than control group, P＜0.05. Among the model groups, F and FA groups were equal in steatosis P＞0.05. FA group was higher than F and A groups at the level of inflammation.3. serum biochemistry index in each group:Compared with control group, ALT, AST in experiment groups were increased markably(P<0.05). ALT, AST in FA group was higher than F and A group, but it was no change in group A and F(P＞0.05).4. lipidemia and serum free fatty acid(FFA):Serum lipid from experiment group rats were increased variously(p＜0.05). Except F and A groups, there were significantly differences in each other groups.5. measuration of antioxygen index in liver tissue:GSH and SOD in experiment groups decreased variously(P＜0.05).Among the model groups, FA group was higher than F and A group, and the latter two groups had no significantly differience(P＞0.05); MDA in experiment groups increased differently(P＜0.05). FA group was higher than other two groups.6. hepatic tissue expression of CYP 2El:The expression of CYP 2El in model groups liver was significantly increased, ??P＜0.05. CYP 2El almost localized on the hepatic cell 3 area, and increased corresponding to the level of steatosis and inflammation.7. expression of CYP 2El mRNA in liver tissue:CYP 2El mRNA in A group was little increased comparing with N group (P＞0.05).FA and F groups increased significantly.Factorial analysis indicated that alcohol had little effect on expression of CYP 2El mRNA, high fat diets had positive effect on expression of CYP 2El mRNA(P=0.00), both high fat diets and alcohol had significantly interaction(P＜0.05).8. correlation analysis of CYP 2El, MDA, steatosis and inflammation in experimentoups:In model groups,CYP 2ElmRNA and MDA had remarkable positive correlation(r=0.983 P＜0.01), however, had a negative correlation with GSH and SOD (r is-0.833 and -0.948respectiely, P＜0.01). CYP 2ElmRNA had positive correlation with steatosis and inflammation (r is 0.618 and 0.966 respectively, P＜0.01).Conclusion:1. Both alcohol and high fat diets are revulsant of liver CYP 2El, and the mechanism is in protein and in DNA level, respectively. Two factors cooperate, and they have interaction on expression of CYP 2El mRNA.2. CYP 2El is concerned with the process of steatosis, inflammation and fibrosis in FLD, and participates in "the course of two hits", by weakening antioxygen factors, increasing ROS, aggravating lipid oxidation.3. CYP 2El is the common pathogenesis ofbothAFLD and NAFLD.
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