家族性肌萎缩侧索硬化症患者及家系成员血中铜/锌超氧化物歧化酶活性及丙二醛水平变化与临床分型的关系

背景不同的铜 /锌超氧化物歧化酶( Copper/Zinc superoxide dismutase, Cu/ZnSOD)基因突变会使家族性肌萎缩侧索硬化 (family amyotropbic lateral sclerosis, FALS)产生不同的临床特征;丙二醛是过氧化脂降解的中间产物,可间接反映 Cu/ZnSOD的活性,但 Cu/ZnSOD活性及丙二醛水平改变与 FALS临床分型之间的关系尚不明确.若能探明前两者与后者的关系,将有助于 FALS的临床分型及亚临床诊断. 目的探讨家族性肌萎缩侧索硬化症患者及家系成员 Cu/ZnSOD活性和丙二醛水平变化及 FALS的临床分型. 设计随机病例对照研究. 地点和对象 1998-09/1999-06共检测 7个家系的 32名成员,其中 3例先证者经中山医科大学第一附属院神经内科确诊( 1995年); 4例经广西医科大学附属第一医院神经内科确诊( 1997～ 1999年).将 32名成员分为 4组汉族血统中有临床表现或有肌电图异常者归为第 1组(共 10例);各项检查均正常者的为第 2组(共 17例).壮族血统家系中有临床表现或肌电图异常者归为第 3组(共 3例);无临床表现、各项检查均正常者归为第 4组(共 2例). 72例对照组(第 5组)均来自 1999-01/1999-12到我院健康体检自愿者,其中男 38例,女 34例,年龄 15～ 59岁,平均 38.2岁. 方法采用生物化学方法测定红细胞内 Cu/ZnSOD活性及丙二醛水平. 主要观察指标外周血 SOD活性及丙二醛水平. 结果第 1组 Cu/ZnSOD活性为( 316.68± 46.15) μ kat/g,丙二醛水平为( 8.08± 1.60) μ mol/L 1 100溶血液,其中,有 4例 Cu/ZnSOD活性低于正常值, 3例丙二醛水平高于正常值,后者与前中的 3例为相同患者,无临床症状.第 2组 Cu/ZnSOD活性为( 351.74± 28.42) μ kat/g,丙二醛水平为( 6.55± 0.87) μ mol/L 1 100溶血液,其中有 2例 Cu/ZnSOD活性低于正常对照组. 6例 Cu/ZnSOD活性低于正常值者及 3例丙二醛水平高于正常值者均集中见于 2个家系,并且与同组其他成员比较下降幅度约 20%.第 3组 Cu/ZnSOD活性为( 351.89± 27.92) μ kat/g,丙二醛水平为( 6.68± 0.59) μ mol/L 1100溶血液,第 4组 Cu/ZnSOD活性为( 351.89± 27.96) μ kat/g,丙二醛水平为( 6.61± 0.69) μ mol/L 1100溶血液,第 3, 4组两项测定值均在正常值范围内.第 5组为健康对照组(共 72例). Cu/ZnSOD活性为( 351.84± 26.76) μ kat/g,丙二醛水平为( 6.69± 0.58) μ mol/L 1100溶血液.第 5组与第 1组比较, F=8.1287,27.8872,P< 0.01.推测其发病类型为 ALS1型. 结论红细胞内 Cu/ZnSOD活性测定及丙二醛水平测定有可能作为 ALS 1型患者及基因携带者的诊断方法之一,并可用于 FALS初步分型及基因检测前的筛查.

Relation of clinical type to the content of malondialdehyde and the activity of copper/zinc superoxide dismutase in patients with familial amyotrophic lateral sclerosis and their family members

BACKGROUND:Studies have indicated an association between familial amyotropbic lateral sclerosis(FALS) and copper/zinc superoxide dismutase(Cu/ZnSOD) gene mutation, and various Cu/ZnSOD gene mutations give rise to various clinical features of FALS.Cu/ZnSOD is a key enzyme for eliminating oxygen free radicals, and malondialdehyde(MDA) is an intermediate product of perexilipoid degradation, which indirectly reflects Cu/ZnSOD activity.However,the association of the changes of Cu/ZnSOD and MDA with the clinical features of FALS has not been defined.The understanding of this association may offer assistance of the clinical classification of FALS and diagnosis of subclinical FALS. OBJECTIVE:To study the Cu/ZnSOD activity and MDA content in the blood of patients with FALS and their family members,and to study the clinical classification of FALS. DESIGN:A randomized case-control trial. SETTING and PARTICIPANTS:Thirty-two subjects from 7 families of FALS were enrolled in this study,with the 3 propositi of them definitely diagnosed in the Department of Neurology, he First Affiliated Hospital of Sun Yat-sen Medical University in 1995 and 4 in the Department of Neurology,the First Affiliated Hospital of Guangxi Medical University between 1997 and 1999.The 32 subjects were divided into four groups:of the 27 subjects of Han nationality, 10 with clinical manifestations or abnormal electromyogram(EMG) were assigned into group 1,and the other 17 normal subjects into group 2; of the 5 subjects of Zhuang nationality,3 with clinical manifestations or abnormal EMG were assigned into group 3,and 2 normal subjects without any clinical manifestations into group 4.Another 72 healthy volunteers receiving routine physical examinations in our hospital between January 1999 and December 1999 were also enrolled as controls, including 38 males and 34 females subjects aged 15-59 years with the mean age of 38.2 years. METHODS:Biochemical methods were used to determine Cu/ZnSOD activity and MDA content in the erythrocytes of all subjects. MAIN OUTCOME MEASURES:Cu/ZnSOD activity and MDA content in peripheral blood. RESULTS:In group 1, the activity of Cu/ZnSOD was(316.68± 46.15) μ kat/g,and the content of MDA was(8.08± 1.60) μ mol/L in 100-fold diluted hemolysis solution, and 4 cases had Cu/ZnSOD activity less than the normal level, among which 3 elevated MDA content, but no clinical manifestations were observed. In group 2, the two measurements were(351.74± 28.42) μ kat/g and(6.55± 0.87) μ mol/L,and 2 cases had lowered Cu/ZnSOD activity, and 6 had lowered whereas 3 had elevated MDA content,in comparison with the normal contents.In the above two groups of Han nationality,the 6 subjects with lowered Cu/ZnSOD activity and 3 with elevated MDA contents who came from two families had measurements significantly decreased by about 20% in comparison with those of the other members in the same group.Cu/ZnSOD activity and MDA content were(351.89± 27.92) μ kat/g and(6.68± 0.59) μ mol/L respectively in group 3,and(351.87± 27.96) μ kat/g and(6.61± 0.69) μ mol/L in the group 4,all within the normal range.In the control group, the activity of Cu/ZnSOD and MDA content were(351.84± 26.76) μ kat/g and(6.69± 0.58) μ mol/L respectively, showing a significant difference with the measurements of group 1(F=8.1287,27.8872,P< 0.01).It was suggested that patients in group 1 had clinical FALS classification of ALS1. CONCLUSION:The determination of Cu/ZnSOD and MDA can be used for diagnosis of ALS1 and ALS1 carriers, also applicable in screening Cu/Zn SOD gene mutation and classification of FALS.