de Man F H, Jonkers I J, Schwedhelm E, Smelt A H, Onkenhout W, van Duyvenvoorde W, Buytenhek R, Leuven J A, Troost R, van Der Laarse A, Princen H M
Department of Cardiology, Internal Medicine Leiden University Medical Center, The Netherlands.
Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2434-40. doi: 10.1161/01.atv.20.11.2434.
Although there is evidence that hyperlipidemia and predominance of small dense low density lipoproteins (LDLs) are associated with increased oxidative stress, the oxidation status in patients with hypertriglyceridemia (HTG) has not been studied in detail. Therefore, we studied urinary levels of F(2)-isoprostanes (8-isoprostaglandin F(2alpha) and 2,3-dinor-5,6-dihydro-8-isoprostaglandin F(2alpha)) and susceptibility of very low density lipoproteins (VLDLs) and LDLs to oxidation ex vivo in 18 patients with endogenous HTG and 20 matched control subjects. In addition, the effects of 6 weeks of bezafibrate therapy were assessed in a double-blind, placebo-controlled, crossover trial. Urinary levels of F(2)-isoprostanes were similar in the HTG and normolipidemic group. Bezafibrate caused an increase in 8-isoprostaglandin F(2alpha) (762+/-313 versus 552+/-245 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.03), whereas 2,3-dinor-5, 6-dihydro-8-isoprostaglandin F(2alpha) levels tended to be increased (1714+/-761 versus 1475+/-606 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.11). VLDLs and LDLs were more resistant to copper-induced oxidation in patients with HTG than in control subjects. Bezafibrate reversed the oxidation resistance to the normal range. In conclusion, these results indicate the following: (1) HTG is associated with normal in vivo oxidative stress and enhanced ex vivo resistance of lipoproteins to oxidation. (2) Bezafibrate reduces the resistance of lipoproteins to copper-induced oxidation and enhances oxidative stress in HTG patients.
尽管有证据表明高脂血症和小而密低密度脂蛋白（LDL）占优势与氧化应激增加有关，但高甘油三酯血症（HTG）患者的氧化状态尚未得到详细研究。因此，我们研究了18例内源性HTG患者和20例匹配的对照受试者尿液中F（2）-异前列腺素（8-异前列腺素F（2α）和2,3-二去甲-5,6-二氢-8-异前列腺素F（2α））的水平，以及极低密度脂蛋白（VLDL）和LDL在体外对氧化的敏感性。此外，在一项双盲、安慰剂对照、交叉试验中评估了苯扎贝特治疗6周的效果。HTG组和血脂正常组尿液中F（2）-异前列腺素水平相似。苯扎贝特导致8-异前列腺素F（2α）升高（苯扎贝特治疗组和安慰剂治疗组分别为762±313 ng/24 h和552±245 ng/24 h；P = 0.03），而2,3-二去甲-5,6-二氢-8-异前列腺素F（2α）水平有升高趋势（苯扎贝特治疗组和安慰剂治疗组分别为1714±761 ng/24 h和1475±606 ng/24 h；P = 0.11）。HTG患者的VLDL和LDL比对照受试者对铜诱导的氧化更具抗性。苯扎贝特将氧化抗性逆转至正常范围。总之，这些结果表明：（1）HTG与体内正常氧化应激以及脂蛋白体外抗氧化性增强有关。（2）苯扎贝特降低了HTG患者脂蛋白对铜诱导氧化的抗性并增强了氧化应激。
