海狗油对非酒精性脂肪肝肝细胞色素P450 2E1表达及与氧化抗氧化关系的影响

Effects of seal oil on the correlation between hepatocyte cytochrome P450 2E1 expression and oxidation, antioxidation in rats with nonalcoholic fatty liver

目的 :研究海狗油对非酒精性脂肪肝肝细胞色素P4 5 0 2E1表达及与氧化抗氧化关系的影响。方法 :于实验d 1一次性皮下注射小剂量四氯化碳并长期喂食高脂饲料复制大鼠脂肪肝模型 ,7周后 ,开始分别口服灌胃 (ig)给予模型组等体积橄榄油 ,阳性药辛伐他汀 4mg·kg-1,海狗油各组ig海狗油0 .5、1.6和 4 .8g·kg-1,每天 1次 ,连续 8周。观察肝组织病理形态的变化和肝细胞色素P4 5 0 2E1的表达 ;测定血清和肝内丙二醛 (MDA)、超氧化物歧化酶 (SOD)以及游离脂肪酸 (FFA)含量的变化。结果 :与脂肪肝模型组比较 ,海狗油不同给药组病理切片苏丹Ⅲ染色和HE染色显示肝细胞的脂变程度明显减轻 ,脂滴减少 ,免疫组化证明肝细胞色素P4 5 0 2E1表达受到不同程度的抑制 ,同时血清及肝内MDA、FFA显著降低 ,SOD活性升高。在模型组和各给药组不同的肝组织内 ,CYP2E1的表达强度及分布的方式存在着差异。结论 :海狗油能显著抑制大鼠脂肪肝CYP2E1的表达 ,减轻脂质过氧化反应。

AIM: To explore the effects of seal oil on the correlation between hepatocyte cytochrome P450 2E1 expression and oxidation, antioxidation in rats with nonalcoholic fatty liver. METHODS: After 7 weeks the fatty liver models were induced by onetime subcutaneous injecting a low dose of carbon tetrachloride on the first day and chronically feeding with high fat diet in rats. The rats in the model group, simvastatin group and different doses seal oil group were taken by olive oil in the same volume of seal oil, 4 mg·kg -1 simvastatin, and 0.5, 1.6 and 4.8 g·kg -1 seal oil respectively once a day for 8 weeks. Changes on pathology of liver and expression of hepatocyte cytochrome P450 2E1 were observed. MDA, SOD and FFA in the liver and serum were measured by biochemical analysis. RESULTS: Compared with model group, the fatty degeneration of liver reduced and a smaller lipid droplet of liver in seal oil group. The hepatocyte cytochrome P450 2E1 expression was inhibited. Meanwhile contents of MDA and FFA were significantly decreased but SOD contents were significantly increased in serum and liver. The intensity and distribution of CYP 2E1 express between rats of model differed. These differences existed in simvastatin group and different doses seal oil group. CONCLUSION: Seal oil can inhibit the hepatocyte cytochrome P450 2E1 expression in rats with fatty liver and reduce lipid peroxidation. There is genetic polymorphism of cytochrome P450 2E1 between rats.