高脂血症患者氧化修饰低密度脂蛋白对内皮依赖性血管舒张的影响

Effect of oxidized low-density lipoprotein on endothelium-dependent relaxation in hyperlipidemic patients

目的:探讨氧化修饰低密度脂蛋白(Ox-LDL)对血管舒张的影响及高脂血症男性患者易患动脉粥样硬化(AS)的机制。方法:采用Cu2+对13例健康自愿者及29例高脂血症患者的低密度脂蛋白(LDL)进行氧化修饰,硫代巴比妥酸法测定丙二醛(MDA)含量,Bartlett法测定溶血卵磷脂(LPC)含量,乙酰胆碱诱发血管舒张。结果:健康人和高脂血症患者血浆LDL被氧化修饰后与修饰前比较MDA含量显著增高(P<0.01);两组Ox-LDL中的LPC水平均明显高于各自天然低密度脂蛋白(N-LDL)中的LPC水平(P<0.05);且健康人及高脂血症男性患者N-LDL中的LPC含量与女性基本相同,但两组男性Ox-LDL中的LPC含量高于女性(P<0.05),男性高脂血症患者Ox-LDL的LPC含量最高;两组Ox-LDL均明显抑制血管内皮依赖性舒张,与女性相比,健康男性Ox-LDL抑制血管舒张程度略强,但高脂血症男性患者Ox-LDL抑制血管舒张程度明显增强。高脂血症男性及女性患者Ox-LDL的抑制血管舒张效应与LPC量呈正相关(r=0.592,P<0.05;r=0.816,P<0.05)。结论:男性高脂血症患者易患AS可能与Ox-LDL增加LPC含量及抑制内皮依赖性血管舒张有关。

Objective To study the effecet of oxidized low-density lipoprotein （Ox-LDL） on endothelium-dependent relaxation and mechanism of susceptibility to atherosclerosis （AS） in hyperlipdemic male patients. Methods LDL isolated from 13 normal patients and 29 hyperlipidemic patients were modified by CuSO4. The amount of malondialdehyde （MDA） was measured by TBARS. The amount of lysophosphatidylcholine （LPC） was determined by the Bartlett. Endothelium-dependent relaxation was produced by acetylcholine. Results After LDL from normal and hyperlipidemic patients were modified by CuSO4, the amount of MDA was increased （P〈0. 01）. LPC in Ox- LDL in two groups were higher than those in their respective native LDL （N-LDL）. N-LDL contained similar levels of LPC in males and females in two groups, but Ox-LDL from males produced more LPC than that from females in both groups （P〈0.05）, Ox-LDL from males of hyperlipidemic patients contained the highest level of LPC. Ox- LDL from males and females in both groups inhibited endothelium-dependent relaxation. In hyperlipidemic patients, Ox-LDL from males caused greater impairment of endothelium-dependent ralaxation than that from females, the effect of gender was minimal within the normal group. Correlation analysis indicated that the degree of impairment of endothelium-dependent relaxation of male and female hyperlipidemic patients was correlated with the production of LPC during oxidation, （r=0. 592, P〈0. 05; r=0. 816, P〈0.05）. Conclusion The mechanism of susceptibility to AS in hyperlipdemic male patients is related with the increase of LPC production and greater endothelial dysfunction in Ox-LDL.