Ezetimibe Impairs Uptake of Dietary Cholesterol Oxidation Products and Reduces Alterations in Hepatic Cholesterol Metabolism and Antioxidant Function in Rats
Ezetimibe Impairs Uptake of Dietary Cholesterol Oxidation Products and Reduces Alterations in Hepatic Cholesterol Metabolism and Antioxidant Function in Rats
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DOI：
10.1007/s11745-013-3790-6
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发表时间：
2013-06-01
期刊：
影响因子：
1.9
通讯作者：
Osada, Kyoichi
中科院分区：
文献类型：
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作者：
Terunuma, Shoichiro;Kumata, Noriko;Osada, Kyoichi
膳食胆固醇氧化产物（COP）会引起各种不良反应，包括动脉粥样硬化的发展、脂质代谢的调节和抗氧化系统的不利变化。因此，我们研究了依折替米（一种胆固醇吸收抑制剂）对饲喂COP大鼠肝脏胆固醇代谢和抗氧化系统下调的影响。大鼠分别饲喂含0.3% COP的纯化饲粮（含或不含依折麦比（0.07 mg/100 g体重））27天。依折麦布通过促进COP排泄到粪便中，降低了血浆和肝脏中的COP水平。由此可见，饲粮中添加COP增加了动脉硬化指数，降低了肝脏胆固醇生物合成转录物mRNA的表达。此外，COP加依折麦比的血浆铁还原能力也明显高于单独饲喂COP的大鼠。最后，我们还观察到依折替米贝增强了饲喂COP大鼠肝脂肪酸合成的下调作用。由此可见，ezetimibe通过抑制膳食中COP从小肠的吸收，可能对膳食中COP对肝脏中胆固醇和脂肪酸代谢的破坏以及抗氧化系统的下调起到预防作用。
Dietary cholesterol oxidation products (COP) induce various adverse effects, including development of atherosclerosis, modulation of lipid metabolism, and unfavorable changes in the antioxidant system. Therefore, we examined the effects of ezetimibe, a cholesterol absorption inhibitor on hepatic cholesterol metabolism and down-regulation of the antioxidant system in rats fed COP. Rats were fed a purified diet containing 0.3 % COP with or without ezetimibe (0.07 mg/100 g body weight) for 27 days. Levels of COP in both the plasma and liver were lowered by ezetimibe through promotion of COP excretion into the feces. Reflecting this effect, an increase in the arteriosclerotic index and a reduction in the mRNA expression of hepatic cholesterol biosynthesis transcripts by dietary COP were observed. Moreover, the ferric reducing ability of the plasma also was significantly higher in rats fed COP plus ezetimibe than in those fed COP alone. Finally, we also observed that ezetimibe enhanced the down-regulation of hepatic fatty acid synthesis in rats fed COP. Thus, ezetimibe, which inhibits the absorption of dietary COP from the small intestine, may exert preventive effects on dietary COP-induced disruption of cholesterol and fatty acid metabolism in the liver and down-regulation of the antioxidant system.