用普罗布考结合入乳糜微粒残余预防氧化能

增加这些粒子的人巨噬细胞摄入和脂质堆积

Moore EH etal. Eur J Biochem. 2004; 271(12):2417-27

研究预防乳糜微粒残余氧化对其在巨噬细胞内的摄入和脂质堆积的影响，使用含有亲脂抗氧化剂普罗布考的类乳糜微粒残余粒子(CRLPs)作为研究对象，巨噬细胞衍生于人单核细胞株THP-1。孵育48小时后，与含普罗布考的CRLPs（pCRLPs）共孵育的THP-1巨噬细胞的总脂含量（x2.2）显著高于不含普罗布考者。这是因为增加了甘油三酯（x2.3）和胆固醇（x1.8）水平，而胆固醇脂水平无明显变化。用荧光素1,1'-双十八烷基3,3,3'3'-四甲基吲哚-羰花青高氯酸盐标记测定细胞对CRLPs和pCRLPs的摄入，表明pCRLPs的摄入较CRLPs快。用[(3)H]油酸和[(3)H]甘油联合测定甘油三酯，在与pCRLPs孵育的巨噬细胞内，甘油三酯的合成也较无普罗布考者增加。但磷脂和胆固醇脂无变化。另外，CRLPs和pCRLPs对涉及脂蛋白摄入的基因范围的mRNA表达的作用无区别，对细胞内脂质代谢和巨噬细胞释放胆固醇的作用也无区别。这些结果说明在乳糜微粒残余内携带的抗氧化剂通过增加粒子的摄入速率和细胞内甘油三酯的合成而增加巨噬细胞内的脂质堆积，但胆固醇脂与此不同，这些作用通过转录后水平的变化而进行。因此，在乳糜微粒残余内携带的抗氧化剂可能促进动脉粥样硬化的产生，而这一点在延缓了循环内残余清除的条件下很可能是特别重要的。

(译者注：该研究似提示纯高甘油三酯血症患者不应使用普罗布考)

Eur J Biochem. 2004 Jun;271(12):2417-27.
 
Protection of chylomicron remnants from oxidation by incorporation of probucol into the particles enhances their uptake by human macrophages and increases lipid accumulation in the cells.

Moore EH, Napolitano M, Avella M, Bejta F, Suckling KE, Bravo E, Botham KM.

Department of Veterinary Basic Sciences, The Royal Veterinary College, London, UK.

The effects of protection of chylomicron remnants from oxidation on their uptake and induction of lipid accumulation in macrophages were investigated using chylomicron remnant-like particles (CRLPs) containing the lipophilic antioxidant drug, probucol, and macrophages derived from the human monocyte cell line, THP-1. The total lipid content of THP-1 macrophages was markedly higher (x2.2) after 48 h of incubation of THP-1 macrophages with CRLPs containing probucol (pCRLPs) when compared to CRLPs without probucol, and this was because of increases in triacylglycerol (x2.3) and cholesterol (x1.8) levels, while cholesteryl ester concentrations were not significantly changed. Determination of the uptake of CRLPs and pCRLPs by the cells using particles labelled with the fluorescent probe 1,1'-dioctadecyl-3,3,3'3'-tetramethylindo-carbocyanine perchlorate showed that pCRLPs are taken up at a faster rate than CRLPs. The synthesis of triacylglycerol, as measured by the incorporation of [(3)H]oleate and [(3)H]glycerol, was also increased in macrophages incubated with pCRLPs as compared to CRLPs without probucol, but phospholipid and cholesteryl ester formation from [(3)H]oleate was unaffected. In addition, no differences between the effects of CRLPs and pCRLPs on the expression of mRNA for a range of genes believed to be involved in lipoprotein uptake, intracellular lipid metabolism and the efflux of cholesterol from macrophages was detected. These results suggest that antioxidants carried in chylomicron remnants enhance lipid accumulation in macrophages by increasing the rate of uptake of the particles and raising the intracellular synthesis of triacylglycerol, but not cholesteryl ester, and that these effects are brought about by changes at the post-transcriptional level. Antioxidants carried in chylomicron remnants therefore may promote the development of atherosclerosis, and this is likely to be particularly important in conditions where clearance of remnants from the circulation is delayed.