白塞病患者中抗氧化修饰低密度脂蛋白(LDL)自身抗体的评估、LDL的氧化易感性、血脂和脂质过氧化氢水平、总抗氧化状态、抗氧化酶活性以及内皮功能障碍。
The evaluation of autoantibodies against oxidatively modified low-density lipoprotein (LDL), susceptibility of LDL to oxidation, serum lipids and lipid hydroperoxide levels, total antioxidant status, antioxidant enzyme activities, and endothelial dysfunction in patients with Behçet's disease.
作者信息
Orem Asim, Yandi Y Emre, Vanizor Birgül, Cimşit Gülseren, Uydu Hüseyin Avni, Malkoç Meltem
机构信息
Department of Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080, Trabzon, Turkey.
出版信息
Clin Biochem. 2002 May;35(3):217-24. doi: 10.1016/s0009-9120(02)00290-4.
OBJECTIVES
Behçet's disease is a multisystem disorder characterized by a chronic inflammation including acute attacks and remission periods. Decreased enzyme activity of the antioxidant system and increased levels of free radicals may have important roles in the damage of tissues observed in the disease period. In addition, the atherogenic tendency of serum lipid, lipoproteins, lipid peroxidation levels and endothelial dysfunction accompany the above mentioned findings. As a consequence of these events, different degrees of low density lipoprotein (LDL) oxidation occur in vivo, and then autoantibodies against oxidized-LDL(AuAb-oxLDL) are produced.
DESIGN AND METHODS
Lipids, lipoproteins, lipid hydroperoxide, AuAb-oxLDL, total antioxidant status (TAS), serum-soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor 1 (PAI-1) levels in serum, the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes and plasma, were determined in 25 patients with Behçet's disease and in 25 healthy volunteers. Also, susceptibility to copper-induced in vitro oxidation of LDL by using lag time, a measure of resistance to oxidation, oxidation rate and extent of oxidation, a measure of diene production in both groups, was studied.
RESULTS
It was observed that lipid hydroperoxide and AuAb-oxLDL levels in patients with Behçet's disease were significantly higher, but erythrocyte SOD, CAT, plasma GSH-Px activities, and TAS were significantly lower than those in healthy subjects. Susceptibility of LDL to oxidation in the patients was found to be increased. Total cholesterol, LDL-C and apo B levels and acute phase reactants were significantly higher, but HDL-C and apo AI levels were significantly lower, in patients when compared to healthy subjects. The levels of AuAb-oxLDL in patients were found to correlate with TAS, total cholesterol, LDL-C, lipid hydroperoxide and erythrocyte SOD activities (r = -0.62, p < 0.01; r = 0.64, p < 0.01; r = 0.55, p < 0.01; r = 0.81, p < 0.01; r = -0.63, p < 0.01, respectively). In addition, lipid hydroperoxide levels were found to correlate with total cholesterol, LDL-C and erythrocyte SOD activities (r = 0.45, p < 0.05; r = 0.45, p < 0.05; r = -0.46, p < 0.05, respectively). PAI-1 and sICAM-1 were found to be increased in the patients and correlated with AuAb-oxLDL and lipid hydroperoxide levels (r = 0.56, p < 0.01; r = 0.67, p < 0.01 and r = 0.59, p < 0.01; r = 0.61, p < 0.01, respectively).
CONCLUSIONS
It was concluded that the observed increase of lipid, lipoproteins, lipid hydroperoxide, susceptibility of LDL to oxidation, autoantibodies against ox-LDL levels and decrease of antioxidant enzyme activities and total antioxidant status and increased secretion of endothelial derivated peptides including sICAM and PAI-1, and their interactions may indicate that there is a tendency to atherothrombotic events in patients with Behçet's disease.
目的
白塞病是一种多系统疾病,其特征为包括急性发作期和缓解期的慢性炎症。抗氧化系统酶活性降低和自由基水平升高可能在疾病期观察到的组织损伤中起重要作用。此外,血清脂质、脂蛋白、脂质过氧化水平的致动脉粥样硬化倾向以及内皮功能障碍伴随上述发现。这些事件的结果是,体内发生不同程度的低密度脂蛋白(LDL)氧化,然后产生针对氧化型LDL的自身抗体(AuAb-oxLDL)。
设计与方法
测定了25例白塞病患者和25名健康志愿者血清中的脂质、脂蛋白、脂质氢过氧化物、AuAb-oxLDL、总抗氧化状态(TAS)、血清可溶性细胞间黏附分子-1(sICAM-1)、纤溶酶原激活物抑制剂1(PAI-1)水平,以及红细胞和血浆中包括谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽还原酶(GR)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)在内的抗氧化酶活性。此外,通过使用滞后时间(一种抗氧化抗性的测量指标)、氧化速率和氧化程度(两组中双烯生成的测量指标)研究了两组中铜诱导的LDL体外氧化敏感性。
结果
观察到白塞病患者的脂质氢过氧化物和AuAb-oxLDL水平显著更高,但红细胞SOD、CAT、血浆GSH-Px活性和TAS显著低于健康受试者。发现患者中LDL的氧化敏感性增加。与健康受试者相比,患者的总胆固醇、LDL-C和载脂蛋白B水平以及急性期反应物显著更高,但HDL-C和载脂蛋白AI水平显著更低。发现患者中AuAb-oxLDL水平与TAS、总胆固醇、LDL-C、脂质氢过氧化物和红细胞SOD活性相关(r分别为-0.62,p<0.01;r = 0.64,p<0.01;r = 0.55,p<0.01;r = 0.81,p<0.01;r = -0.63,p<0.01)。此外,发现脂质氢过氧化物水平与总胆固醇、LDL-C和红细胞SOD活性相关(r分别为0.45,p<0.05;r = 0.45,p<0.05;r = -0.46,p<0.05)。发现患者中PAI-1和sICAM-1升高,并与AuAb-oxLDL和脂质氢过氧化物水平相关(r分别为0.56,p<0.01;r = 0.67,p<0.01和r = 0.59,p<0.01;r = 0.61,p<0.01)。
结论
得出的结论是观察到的脂质、脂蛋白、脂质氢过氧化物增加,LDL氧化敏感性增加,抗氧化型LDL自身抗体水平升高,抗氧化酶活性和总抗氧化状态降低,以及包括sICAM和PAI-1在内的内皮衍生肽分泌增加,及其相互作用可能表明白塞病患者存在动脉粥样硬化血栓形成事件的倾向。