Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
Atherosclerosis. 2013 Sep;230(1):48-51. doi: 10.1016/j.atherosclerosis.2013.06.016. Epub 2013 Jul 4.
Cholesterol and diet-derived oxidized cholesterol are absorbed in the small intestine and eliminated by bile acids. We determined whether ezetimibe, a selective cholesterol absorption inhibitor, changes serum oxidized cholesterol levels.
We measured levels of plant sterols, cholesterol precursors, and oxysterols by gas chromatography-mass spectrometry in 47 hypercholesterolemics and 32 controls. Twenty-four hypercholesterolemics received 10 mg ezetimibe/day for 4 weeks.
Plant sterols were 30-42% higher in hypercholesterolemics than in controls and positively correlated with low-density lipoprotein-cholesterol (LDL-C). Ezetimibe decreased plant sterols by 21-53%, but did not change bile acid synthesis markers. 7β-hydroxycholesterol, a marker for non-enzymatic oxidation of cholesterol, was 66% higher in hypercholesterolemics than controls. Ezetimibe decreased 7β-hydroxycholesterol levels by 15% regardless of LDL-C reduction.
Ezetimibe decreases serum oxidized cholesterol generated by non-enzymatic reactions without impairing bile acid synthesis. Ezetimibe may maintain cholesterol excretion into bile and alleviate the diet-derived oxidative burden.
胆固醇和饮食来源的氧化胆固醇在小肠中被吸收，并通过胆汁酸排出。我们旨在确定选择性胆固醇吸收抑制剂依折麦布是否会改变血清氧化胆固醇水平。
我们通过气相色谱-质谱法测定了 47 名高胆固醇血症患者和 32 名对照者的植物固醇、胆固醇前体和氧化固醇水平。24 名高胆固醇血症患者每天服用 10 毫克依折麦布，持续 4 周。
高胆固醇血症患者的植物固醇比对照组高 30-42%，且与低密度脂蛋白胆固醇（LDL-C）呈正相关。依折麦布使植物固醇降低 21-53%，但不改变胆汁酸合成标志物。胆固醇非酶氧化的标志物 7β-羟基胆固醇在高胆固醇血症患者中比对照组高 66%。依折麦布降低 7β-羟基胆固醇水平 15%，与 LDL-C 降低无关。
依折麦布可降低非酶反应产生的血清氧化胆固醇，而不损害胆汁酸合成。依折麦布可能维持胆固醇排入胆汁，并减轻饮食来源的氧化负担。
