【作者】 章群；

【导师】 叶冬青；

【作者基本信息】 安徽医科大学 ， 流行病与卫生统计学， 2008， 硕士

【摘要】 目的探讨系统性红斑狼疮(systemic lupus erythematosus, SLE)患者脂质过氧化、蛋白质氧化损伤程度以及氧化/抗氧化作用与临床疾病活动指标以及病程进展中组织和器官慢性损伤的关联性。方法病例选用安徽医科大学附属医院风湿科门诊及住院确诊的SLE患者,以性别、年龄匹配的健康献血员为健康对照,参照系统性红斑狼疮疾病活动性指数(systemic lupus erythematosus disease activity index,SLEDAI)自行设计调查问卷,调查病例和对照的一般线性资料、以及病例组的疾病活动情况和临床/实验室资料。应用分光光度法测定SLE患者及正常对照者血浆中蛋白质氧化损伤相关指标(蛋白质羰基和巯基),脂质过氧化指标(丙二醛(malondialdehyde , MDA)),超氧化物歧化酶(superoxide dismutase, SOD)、髓过氧化酶(myeloperoxidase , MPO)和总抗氧化能力(total antioxidant capacity , TOAC)),采用酶联免疫吸附法定性测定SLE患者血浆抗ds-DNA抗体和抗核抗体的水平。病例组和对照组以及病例组间定量资料的比较,符合正态分布者采用t检验;不符合正态分布者,对其进行Mann-Whitney秩和检验。指标间相关分析,正态分布者采用Pearson相关,不符合正态分布者用Spearman等级相关。定性资料的组间比较采用χ2检验。以α=0.05作为检验水准。结果系统性红斑狼疮患者脂质过氧化与蛋白质氧化产物与健康对照组相比差异显著,其中MDA、蛋白质羰基浓度以及MPO活性显著升高,蛋白质巯基浓度、活性显著降低,且与疾病活动相关指标有一定关联。抗dsDNA抗体阳性组血浆蛋白质巯基浓度、SOD活性显著低于阴性组,合并肾脏损伤或心血管损伤的SLE病人脂质过氧化和蛋白质氧化程度显著高于无上述合并症的SLE病人。结论处于疾病活动状态的SLE患者,存在一定程度的脂质过氧化和蛋白质氧化损伤现象,且氧化损伤程度与疾病活动正相关。合并肾脏损伤以及心血管损伤与患者机体的氧化应激状态也存在一定关联,提示脂质过氧化以及蛋白质氧化损伤对以静脉微血管损伤、血管通透性改变为病理基础的SLE慢性器官损伤的发病机制可能存在一定的作用。更多还原

【Abstract】 Objective To explore oxidative/anti-oxidative status(lipid oxidation, protein oxidative damage and antioxidant enzymes) in systemic lupus erythematosus (SLE), and to find the relationship between oxidation/anti-oxidation indexes and clinical indicators.Method SLE patients were in- and out- patients of the Rheumatology Department in the First Affiliated Hospital, and health volunteers were recruited as controls. General information, chemical examination results and data of organ or system damage were collected by self-designed questionnaire. Here we have examined plasma oxidative damage indexs(such as malondialdehyde, protein carbonyl and protein thiol), superoxide dismutase(SOD), myeloperoxidase(MPO) and total antioxidant capacity (TOAC) in SLE patients and healthy controls. Levels of anti-double-stranded DNA (anti-dsDNA) and antinuclear antibody (ANA) were quantified by enzyme-linked immunosorbent assay. Variables were tested for skewness, and skewed continuous variables were logarithmically transformed. When appropriate, nonparametric tests (Mann-Whitney U test) were used for comparisons between the groups, whereas student’s t-test was used for normally distributed variables. Spearman’s rank correlation was used to calculate correlation coefficients between lipid Peroxidation, protein oxidation, anti-oxidation and clinical/laboratory indexes.Results Compared with control subjects, SLE patients exhibited elevated levels of MDA(malondialdehyde) and protein carbonyls and decreased levels of protein thiols and activities of SOD. Plasma protein thiols levels and activities of SOD were lower in anti-dsDNA antibody(+) groups compared with anti-dsDNA antibody(-) groups in SLE patients. Lipid peroxidation and protein oxidation were significantly higher in SLE patients with nephropathy or cardiovascular complications than those without such complications patients. Conclusion We found elevated levels of multiple markers of protein oxidation and degraded activities of antioxidant enzymes in plasma from SLE patients compared with controls, and these levels correlated with disease activity. The relationships between cardiac injury, nephropathy and oxidative stress were confrimed in SLE patients, which suggest oxidative stress may play a important role in the pathogenesis of chronic organ damage in SLE.更多还原