Metabolic Research Centre (T.W.K.N., E.M.M.O., G.F.W., D.C.C., P.H.R.B.), School of Medicine and Pharmacology, and Faculty of Engineering (P.H.R.B.), Computing and Mathematics, Perth, Western Australia, Australia; and Metabolomics Laboratory (T.W.K.N., J.M.W., P.J.M.), Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
J Clin Endocrinol Metab. 2014 Nov;99(11):E2335-40. doi: 10.1210/jc.2014-1665. Epub 2014 Aug 20.
Statins are effective cholesterol-lowering agents that reduce cardiovascular disease risk but also have pleiotropic effects that may extend to other lipid classes.
The purpose of this article was to investigate, in a post hoc analysis, the dose-dependent effects of rosuvastatin on plasma sphingolipids and phospholipids in men with the metabolic syndrome.
Subjects (n = 12) were studied in a randomized, double-blind, triple-crossover trial of a 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week washouts between treatments. Plasma sphingolipid profiling was determined by liquid chromatography electrospray ionization-tandem mass spectrometry.
Rosuvastatin at 10 mg/d (R10) and 40 mg/d (R40) significantly (all P < .001 unless stated otherwise) lowered plasma cholesterol (-34% and -42% [% change with R10 and with R40, respectively]), low-density lipoprotein cholesterol (-49% and -57%) and triglyceride (-24%, P =.03 and -42%) concentrations. Compared with placebo, R10 and R40 significantly decreased the plasma levels of total sphingolipids including those of ceramide (-33% and -37%), sphingomyelin (-27% and -31%), monohexosylceramide (-40% and -47%), dihexosylceramide (-31% and -34%), and trihexosylceramide (-29% and -31%), and GM3 gangliosides (-29% and -26%), lysophosphatidylcholine (-32% and -37%), alkylphosphatidylcholine (-19% and -19%), phosphatidylcholine (-17% and -19%), alkenylphosphatidylcholine (plasmalogen) (-20% and -22%), alkylphosphatidylethanolamine (-20%, P =.008 and -24%, P =.02), alkenylphosphatidylethanolamine (plasmalogen) (-24%, P =.003 and -23%, P =.007), phosphatidylglycerol (-24%, P =.07, -31%, P =.046), and phosphatidylinositol (-34% and -40%). No significant changes were found with phosphatidylethanolamine and phosphatidylserine. Significant dose effects were found with the majority of the plasma sphingolipids, whereas only phosphatidylcholine, lysophosphatidylcholine, alkylphosphatidylcholine, alkenylphosphatidylcholine (plasmalogen), and phosphatidylinositol had significant dose effects. Similar changes were found with plasma sphingolipids when results were normalized to the total phosphatidylcholine concentration.
Rosuvastatin dose-dependently lowers plasma sphingolipids and phospholipids, independent of low-density lipoprotein lowering, in men with the metabolic syndrome.
他汀类药物是有效的降脂药物，可降低心血管疾病风险，但也具有多效性，可能扩展到其他脂质类。
本文旨在通过事后分析，研究瑞舒伐他汀对代谢综合征男性患者血浆鞘脂和磷脂的剂量依赖性影响。
12 名受试者参加了一项为期 5 周的随机、双盲、三交叉试验，接受安慰剂或瑞舒伐他汀（10 或 40mg/天）治疗，每 2 周洗脱一次。通过液相色谱电喷雾串联质谱法测定血浆鞘脂谱。
瑞舒伐他汀 10mg/d（R10）和 40mg/d（R40）显著（均 P<.001，除非另有说明）降低了血浆胆固醇（-34%和-42%[分别为 R10 和 R40 的变化百分比]）、低密度脂蛋白胆固醇（-49%和-57%）和甘油三酯（-24%，P=.03 和-42%）浓度。与安慰剂相比，R10 和 R40 显著降低了总鞘脂的血浆水平，包括神经酰胺（-33%和-37%）、鞘磷脂（-27%和-31%）、单己糖神经酰胺（-40%和-47%）、二己糖神经酰胺（-31%和-34%）和三己糖神经酰胺（-29%和-31%），以及 GM3 神经节苷脂（-29%和-26%）、溶血磷脂酰胆碱（-32%和-37%）、烷基磷脂酰胆碱（-19%和-19%）、磷脂酰胆碱（-17%和-19%）、烯基磷脂酰胆碱（溶血磷脂酰乙醇胺）（-20%和-22%）、烷基磷脂酰乙醇胺（溶血磷脂酰乙醇胺）（-20%，P=.008 和-24%，P=.02）、烯基磷脂酰乙醇胺（溶血磷脂酰乙醇胺）（-24%，P=.003 和-23%，P=.007）、磷脂酰甘油（-24%，P=.07，-31%，P=.046）和磷脂酰肌醇（-34%和-40%）。未发现磷脂酰乙醇胺和磷脂酰丝氨酸有显著变化。大多数血浆鞘脂均有显著的剂量效应，而只有磷脂酰胆碱、溶血磷脂酰胆碱、烷基磷脂酰胆碱、烯基磷脂酰胆碱（溶血磷脂酰乙醇胺）和磷脂酰肌醇有显著的剂量效应。当将结果归一化为总磷脂酰胆碱浓度时，血浆鞘脂也有类似的变化。
瑞舒伐他汀可剂量依赖性降低代谢综合征男性患者的血浆鞘脂和磷脂，且与降低 LDL 无关。
