背景：研究普罗布考和植物甾醇混合物（FCP-3PI）对载脂蛋白E敲除小鼠动脉粥样硬化损伤形成，血浆脂蛋白，肝脏和脂蛋白脂肪酶，抗氧化物酶活性以及血浆纤维蛋白原的影响。

    方法与结果：三组小鼠（每组8只）分别经含9%脂肪的饮食（对照组），该饮食中分别添加1%(wt/wt)普罗布考（普罗布考组）或2% (wt/wt) FCP-3PI (FCP-3PI组)饲养20周。普罗布考组动脉粥样硬化的损伤面积为对照组的三倍，而在FCP-3PI组损伤面积减小一半。普罗布考治疗产生的普罗布考高血浆浓度与损伤面积相关(r=0.69)。普罗布考治疗组HDL胆固醇减少(>75%)，而在FCP-3PI组有轻微增加(14%)。两组中后肝素脂蛋白脂肪酶（LPL）的活性均显著降低，但仅有FCP-3PI使肝酯酶活性显著降低。与对照组相比，普罗布考治疗组血浆纤维蛋白原增加42%，FCP-3PI组增加19%。普罗布考显著增加血浆谷胱甘肽还原酶，谷胱甘肽过氧化物酶以及超氧化物歧化酶活性（P<0.05）。与apoE-KO小鼠不同，野生小鼠经普罗布考相同剂量和相同时间饲养未发现普罗布考导致的动脉粥样硬化产生。

    结论：FCP-3PI在apoE-KO小鼠中的抗动脉粥样硬化作用与其增加HDL胆固醇含量，降低肝脂肪酶活性和血浆纤维蛋白原的作用有关。普罗布考的促动脉粥样硬化作用可能与其增加血浆纤维蛋白原，降低HDL胆固醇含量和LPL活性的作用有关，或者普罗布考的直接毒性与它的高血浆浓度有关。研究表明抗氧化剂和降胆固醇药物普罗布考在此动物模型中不能预防动脉粥样硬化。

    BACKGROUND: The effects of probucol and a phytosterol mixture (FCP-3PI) on atherosclerotic lesion formation, plasma lipoproteins, hepatic and lipoprotein lipase activities, antioxidant enzyme activities, and plasma fibrinogen were investigated in apolipoprotein E-knockout (apoE-KO) mice.

    METHODS AND RESULTS: Three groups of 8 mice were fed a diet containing 9% (wt/wt) fat (controls) or the foregoing diet supplemented with either 1% (wt/wt) probucol (the probucol group) or 2% (wt/wt) FCP-3PI (the FCP-3PI group) for 20 weeks. Compared with controls, atherosclerotic lesion size was 3 times greater in the probucol group, whereas it was decreased by half in the FCP-3PI group. Probucol treatment resulted in high plasma probucol concentrations, which correlated (r=0.69) with the lesion area. HDL cholesterol was reduced (>75%) in the probucol group and slightly increased (14%) in the FCP-3PI-treated group. Postheparin lipoprotein lipase (LPL) activity was significantly reduced in both treatment groups, but only FCP-3PI significantly decreased hepatic lipase activity. Plasma fibrinogen was increased 42% by probucol and decreased 19% by FCP-3PI relative to controls. Probucol significantly increased plasma glutathione reductase, glutathione peroxidase, and superoxide dismutase activities (P<0.05). In contrast to findings in apoE-KO mice, there was no probucol-induced atherosclerosis in their wild-type counterparts fed the same dose for the same period of time.

    CONCLUSIONS: Antiatherogenic activity of FCP-3PI in apoE-KO mice is associated with an increase in HDL cholesterol concentration along with decreases in hepatic lipase activity and plasma fibrinogen concentrations. Proatherogenic effects of probucol may be related to increased plasma fibrinogen, decreased HDL cholesterol concentrations along with decreased LPL activity, or its direct "toxicity" due to very high plasma concentration. Our studies demonstrate that the antioxidant and cholesterol-lowering properties of probucol do not prevent atherogenesis in this particular animal model.