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机构地区:[1]中国药品生物制品检定所生化药品与基因工程药物室,北京100050
出 处:《中国临床药理学与治疗学》2005年第5期518-521,共4页Chinese Journal of Clinical Pharmacology and Therapeutics
摘 要:目的:探讨海狗油抑制脂肪肝的作用机理。方法:小剂量四氯化碳合并高脂饲料复制大鼠脂肪肝模型7周后,模型组灌胃(ig)给予等体积橄榄油;辛伐他汀组给予辛伐他汀4mg·kg-1·d-1,海狗油低、中、高剂量组ig海狗油0.5、1.6、4.8g·kg-1·d-1,连续8周,正常大鼠作为空白组。测定肝脂、肝内前列环素的代谢产物(6ketoPGF1α)与血栓素A2的代谢产物(TXB2)含量,观察脂质过氧化作用和组织学检查结果。结果:海狗油各组肝细胞内TXB2含量降低,6ketoPGF1αTXB2比值增加,超氧化物歧化酶(SOD)活性升高,甘油三脂(TG)、总胆固醇(TC)、丙二醛(MDA)、游离脂肪酸(FFA)含量显著降低,组织学检查显示肝内脂变减轻,细胞色素P4502E1(CYP2E1)免疫组织化学染色显色指数减小。结论:海狗油使实验性脂肪肝的肝脂和肝内血栓素A2的代谢产物减少,即抑制肝脂合成、促进肝脂代谢(直接作用);使肝内血液粘度减少、血液流动性增加(间接作用),从而对实验性脂肪肝有抑制作用;同时海狗油使MDA含量降低、SOD活性升高而有抗氧化作用。AIM: To study the inhibition effects of seal oil on fatty liver in rats. METHODS: A low dose of carbon tetrachloride and high fat diet chronically feed was given to five groups (n=10 in each) of male Wistar rats for 7 weeks to induce the model of fatty liver. Then the five groups were orally administered olive oil, simvastatin 4 (mg·kg^(-1)·d^(-1)), seal oil (0.5), (1.6) or (4.8) (g·kg^(-1)·d^(-1)) for other 8 weeks,respectively. The untreated control group received only normal feed. The liver lipid, production of prostacyclin and thromboxane A_2, lipid superoxidation parameters were measured to compare with the changes. The pathology was evaluated. RESULTS: The ratio of 6-keto-PGF_(1α)/TXB_2 were significantly increased in seal oil group due to decrease TXB_2 and increase 6-keto-PGF_(1α) in liver when compared with those in olive oil group (model group) (P<(0.01)). Liver TC, TG, FFA and MDA concentrations were significantly decreased in the seal oil groups when compared with those in model group (P<(0.01)), but SOD concentration increased (P<(0.01)). Pathology showed that seal oil markedly improved fatty liver and the reduction of index analyzed from CYP2E1 express (P<(0.01)). CONCLUSION: Seal oil inhibits fatty changes of the liver by both direct effects of inhibition the synthesis of liver lipid and modulating lipid metabolism and indirect effects of increase the hepatic blood flow due to decrease the TXA_2 concentration and blood viscosity. In addition, seal oil shows anti-lipid superoxidation by decreasing MDA concentration.
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