Kiss Emese, Seres Ildikó, Tarr Tünde, Kocsis Zsolt, Szegedi Gyula, Paragh György
Third Department of Internal Medicine, Medical and Health Science Center University of Debrecen, Debrecen, Hungary.
Ann N Y Acad Sci. 2007 Jun;1108:83-91. doi: 10.1196/annals.1422.009.
Excessive lipid peroxidation is a major factor of accelerated atherosclerosis, observed in patients with systemic lupus erythematosus (SLE). We aimed at the present study to determine the paraoxonasel (PON1) and arylesterase activities, and lipid-profile in 37 SLE patients and 30 age-/sex-matched controls. Association was analyzed between PON1 activity and SLEDAI, CRP, anti-oxLDL, and antiphospholipid antibody (aPL) levels, steroid dose, and atherothrombotic events. The age of patients was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, SLEDAI 2 (0-15). PON1 and arylesterase activities were measured spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Phenotypic distribution of PON1 was determined by dual substrate method. We measured antioxLDL and aPL levels by ELISA, the CRP by automated immunoassay. PON1 activity (121.9 +/- 65.9 U/mL) was reduced significantly (P < 0.001) in SLE as compared to control (188.1 +/- 78.9 U/mL), but arylesterase activity was not different. A negative correlation was found between PON1 activity and age. PON1 activity did not correlate with other measured parameters. Reduced PON1 activity associated with clinical atherothrombotic complications (P < 0.01). High activity BB phenotype was not present in SLE. Lipid parameters (TC, LDL-C, HDL-C, ApoAI, and ApoB) were within normal range in both groups. Results indicated reduced PON1 activity in lupus patients despite long disease duration and low inflammatory activity, and it was evidenced as a risk for atherosclerotic complications. As the arylesterase activity was normal, further examinations are required to find other mechanisms, such as anti-PON1 antibodies, genetic polymorphisms, and difference in distribution of HDL-subfractions or enzyme abnormalities in HDL remodeling.
脂质过氧化过度是系统性红斑狼疮（SLE）患者加速动脉粥样硬化的主要因素。在本研究中，我们旨在测定37例SLE患者和30例年龄及性别匹配的对照者的对氧磷酶1（PON1）和芳基酯酶活性以及血脂谱。分析了PON1活性与SLE疾病活动指数（SLEDAI）、C反应蛋白（CRP）、抗氧化型低密度脂蛋白（oxLDL）和抗磷脂抗体（aPL）水平、类固醇剂量以及动脉粥样硬化血栓形成事件之间的关联。患者年龄为40.8±13.9岁，随访时间为6.7±6.2年，SLEDAI为2（0 - 15）。分别以对氧磷和苯乙酸为底物，用分光光度法测定PON１和芳基酯酶活性。采用双底物法确定PON1的表型分布。通过酶联免疫吸附测定法（ELISA）检测抗oxLDL和aPL水平，用自动免疫分析法检测CRP。与对照组（188.1±78.9 U/mL）相比，SLE患者的PON1活性（121.9±65.9 U/mL）显著降低（P < 0.001），但芳基酯酶活性无差异。发现PON1活性与年龄呈负相关。PON1活性与其他测量参数无相关性。PON1活性降低与临床动脉粥样硬化血栓形成并发症相关（P < 0.01）。SLE患者中不存在高活性BB表型。两组的血脂参数（总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白AI和载脂蛋白B）均在正常范围内。结果表明，尽管疾病持续时间长且炎症活动度低，但狼疮患者的PON1活性仍降低，这被证明是动脉粥样硬化并发症的一个风险因素。由于芳基酯酶活性正常，需要进一步检查以寻找其他机制，如抗PON1抗体、基因多态性以及高密度脂蛋白亚组分分布差异或高密度脂蛋白重塑中的酶异常。
