目的 观察载脂蛋白A-Ⅰ (apoA-Ⅰ)模拟肽L-4F对高脂喂养apoE缺失小鼠HDL抗炎、抗氧化功能的影响,探讨L-4F的抗动脉粥样硬化(AS)机制.方法 8周龄C57BL/6J小鼠18只,普通饲料喂养作为对照组；8周龄apoE缺失小鼠30只,高脂饲料喂养,喂养4周后,随机处死2种小鼠各6只,检测相应指标作为研究基线(第4周).其余apoE缺失小鼠随机分为AS组和L-4F组[L-4F 1 mg/(kg·d)腹腔注射)],每组12只.实验第8、16周末取标本测定血脂水平、血清对氧磷酯酶1(PON1)、髓过氧化物酶(MPO)活性、高敏C反应蛋白(hs-CRP)含量及HDL炎症指数(HⅡ),观察主动脉斑块面积.结果 实验16周后,与AS组比较,L-4F组血脂水平无明显变化,血清PON1活性明显升高,MPO活性、hs CRP、HⅡ显著下降,主动脉斑块/血管内膜表面积比值明显减小(P＜0.05,P＜0.01).结论 L4F可通过升高PON1活性、降低MPO活性,抑制炎性反应、降低HⅡ等,改善HDL抗炎抗氧化功能,从而减少主动脉内中膜厚度和斑块面积,发挥抗AS作用.%Objective To study the effect of L-4F on anti-oxidant and anti inflammatory functions of HDL in apoE deficit mice fed with high fat diets.Methods Eighteen male C57BL/6J mice aged 8 weeks served as a control group and 30 male apoE deficit mice aged 8 weeks served as an experimental group.The rats in control group were fed with normal diets and those in experimental group were fed with high-fat diets for 4 weeks.Six mice in each group were then killed.The rest apoE deficit mice were randomly divided into (AS) group (n=12) and L 4F group (n=12) with L-4F injected into the abdominal cavity at the dose of 1 mg/(kg · d).The serum lipid and hs-CRP levels,paraoxonase 1 (PON 1) and myeloperoxidase (MPO) activity,HDL inflammatory index and erea of aorta plaques were measured at the end of weeks 8 and 16,respectively.Results No significant difference was found in serum lipid level between AS group and L-4F group,the serum PON-1 activity was significantly higher whereas the MPO activity,serum hs-CRP level,HDL inflammatory index,and the ratio between the area of aorta plaques and the surface area of aorta intima were significantly lower in L-4F group than in AS group at the end of week 16 (P＜0.05,P＜0.01).Conclusion L-4F can improve the anti-oxidant and anti-inflammatory functions of HDL,reduce the atorta intima thicknes and the area of aorta plaques,and prevent athrosclerosis by increasing the PON-1 activity,reducing the MPO activity,inhibiting the inflammatory reactions and decreasing the HDL inflammatory index.
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