Zeman M, Zák A, Tvrzická E, Konárková M, Stípek S
IV. interní klinika 1. LF UK a VFN, Praha.
Cas Lek Cesk. 2002 Apr 12;141(7):211-6.
Meta-analyses of epidemiological studies proved that hypertriacylglycerolemia (HTAG) is an independent CHD risk factor. The VLDL lipoproteins, which are the main TAG carrier, are precursors of atherogenic LDL and their increased concentration is related to the decrease of antiatherogenic HDL, increased ratio of small, dense LDL and represents one of the causes of the endothelial dysfunction. According to some authors, HTAG is one of the factors of the oxidation stress.
45 patients of the studied group received 200 mg of micronized fenofibrate per day for six weeks. Before the beginning and after the end of treatment, following examinations were carried out: concentration of plasma lipids, lipoproteins, and apolipoproteins, composition of fatty acids (FA) in main lipid plasma classes and LDL (phosphatidylcholine--PC, TAG, cholesteryl esters--CE) and lipoperoxidation in VLDL and LDL, isolated by preparative ultracentrifugation.
In plasma, the treatment of HTAG led to a significant decrease of TC, TAG and apo-B concentration and to the increase of cholesterol concentration in HDL and in both HDL2 and HDL3 subfractions. In isolated LDL particles we observed a decrease of the TAG portion (by 25%) together with significant lag phase prolongation (by 33%, P < 0.05) and peak time retardation (by 24%, P < 0.05). In VLDL particles the concentration of cholesterol became smaller (by 28%), TAG (by 26%), phospholipids (by 28%) (in all groups P < 0.005) and the lag phase became significantly longer (by 16%, P < 0.01). Treatment with fenofibrate significantly reduced the linoleic acid (18:2n-6) in PC and TAG plasma, CE and TG LDL, in a higher ratio of palmitoleic acid (16:1n-7) in CE LDL, oleic (18:1n-9) in PC LDL, in significant concentration of total monoenic FA in PC and CE LDL and to a significant increase of the concentration of myristic acid (14:0) in CE and myristic and stearic acids (18:0) in TAG LDL. From our results it is possible to conclude that the six-week long treatment of HTAG with micronized phenofibrate led to significant modification of LDL and VLDL composition accompanied by their lower lipoperoxidation indexes. These favourable changes in oxidability were accompanied with changes in the composition of FA in CE, TAG and PC plasma as well as LDL.
流行病学研究的荟萃分析证明,高甘油三酯血症(HTAG)是冠心病的独立危险因素。极低密度脂蛋白(VLDL)是主要的甘油三酯载体,是致动脉粥样硬化低密度脂蛋白(LDL)的前体,其浓度升高与抗动脉粥样硬化高密度脂蛋白(HDL)降低、小而密LDL比例增加有关,是内皮功能障碍的原因之一。一些作者认为,HTAG是氧化应激因素之一。
研究组45例患者每天服用200mg微粒化非诺贝特,持续六周。在治疗开始前和结束后,进行了以下检查:血脂、脂蛋白和载脂蛋白浓度;主要血脂类和LDL中脂肪酸(FA)的组成(磷脂酰胆碱-PC、甘油三酯-TAG、胆固醇酯-CE);通过制备性超速离心分离的VLDL和LDL中的脂质过氧化。
在血浆中,HTAG治疗导致总胆固醇(TC)、甘油三酯(TAG)和载脂蛋白B(apo-B)浓度显著降低,HDL、HDL2和HDL3亚组分中的胆固醇浓度升高。在分离的LDL颗粒中,我们观察到TAG部分减少(25%),同时显著的延迟期延长(33%,P<0.05)和峰值时间延迟(24%,P<0.05)。在VLDL颗粒中,胆固醇浓度降低(28%),TAG降低(26%),磷脂降低(28%)(所有组P<0.005),延迟期显著延长(16%,P<0.01)。非诺贝特治疗显著降低了PC和TAG血浆、CE和TG LDL中的亚油酸(18:2n-6),CE LDL中棕榈油酸(16:1n-7)比例升高,PC LDL中油酸(18:1n-9)升高,PC和CE LDL中总单不饱和FA浓度显著升高,CE中肉豆蔻酸(14:0)和TAG LDL中肉豆蔻酸及硬脂酸(18:0)浓度显著增加。从我们的结果可以得出结论,用微粒化非诺贝特对HTAG进行六周的治疗导致LDL和VLDL组成发生显著改变,同时其脂质过氧化指数降低。这些氧化能力的有利变化伴随着CE、TAG和PC血浆以及LDL中FA组成的变化。