Department of Neurology, Sanjay Gandhi Post Graduate medical Sciences, Lucknow, India.
Department of Neurology, Sanjay Gandhi Post Graduate medical Sciences, Lucknow, India.
J Neuroimmunol. 2014 Sep 15;274(1-2):141-8. doi: 10.1016/j.jneuroim.2014.06.013. Epub 2014 Jun 24.
Free copper in Wilson disease (WD) is toxic and may reduce antioxidant, increase oxidative stress marker and thereby cytokine release and excitotoxic injury, but there is paucity of studies in humans. We report oxidative stress markers, cytokines and glutamate in neurologic WD and correlate these with their clinical severity, laboratory findings and extent of Magnetic resonance imaging (MRI) changes.
29 patients with neurologic WD and 9 asymptomatic WD siblings were included and their clinical, treatment history, disease severity, biochemical findings and MRI changes were noted. Glutathione (GSH), total antioxidant capacity (TAC) and malonodialdehyde (MDA) were measured by spectrophotometer, cytokines by cytokine bead array and glutamate by the fluorometer.
In WD patients, the glutathione (mean±SEM, 2.20±0.06 vs. 2.73±0.04mg/dl, P<0.001) and TAC (1.70±0.03 vs. 2.29±0.02 Trolox_Eq_mmol/l, P<0.001) were reduced, and MDA and glutamate (23.93±0.54 vs. 19.96±0.27μmol/l; P<0.001) were increased (4.7±0.11 vs. 3.03±0.52nmol/ml, P<0.001) compared to controls. The serum IL6 {median (IQRs), 9.42(10.92) vs. 5.2(5.34) pg/ml; P=0.001}, IL8 {12.37(10.92) vs. 5.63(5.52) pg/ml; P<0.001}, IL10 {8.33(8.3) vs. 2.05(1.37) pg/ml; P=0.001} and TNFα {6.14(8.95) vs. 3.61(3.58) pg/ml; P<0.001} were also increased in WD patients compared to controls. These changes were more marked in the neurologic WD compared to asymptomatic WD and in the untreated compared to treated patients. TAC correlated with duration of illness, serum free copper, 24hour urinary copper and serum ceruloplasmin, and glutamate with MDA, TNFα, ceruloplasmin and 24-hour urinary copper.
In WD patients, antioxidants are reduced and MDA, cytokines and glutamate are increased which are more marked in symptomatic neurologic WD than asymptomatic patients.
威尔逊病（WD）中的游离铜具有毒性，可能会降低抗氧化剂水平，增加氧化应激标志物，从而导致细胞因子释放和兴奋毒性损伤，但目前人类对此研究较少。我们报告了神经 WD 中的氧化应激标志物、细胞因子和谷氨酸，并将其与临床严重程度、实验室发现和磁共振成像（MRI）变化相关联。
纳入 29 例神经 WD 患者和 9 例无症状 WD 同胞，并记录其临床、治疗史、疾病严重程度、生化发现和 MRI 变化。采用分光光度计测量谷胱甘肽（GSH）、总抗氧化能力（TAC）和丙二醛（MDA），采用细胞因子珠阵列测量细胞因子，采用荧光计测量谷氨酸。
WD 患者的谷胱甘肽（均值±SEM，2.20±0.06 与 2.73±0.04mg/dl，P<0.001）和 TAC（1.70±0.03 与 2.29±0.02 Trolox_Eq_mmol/l，P<0.001）降低，MDA 和谷氨酸（23.93±0.54 与 19.96±0.27μmol/l；P<0.001）升高（4.7±0.11 与 3.03±0.52nmol/ml，P<0.001），与对照组相比。血清 IL6（中位数（IQR），9.42（10.92）与 5.2（5.34）pg/ml；P=0.001）、IL8（12.37（10.92）与 5.63（5.52）pg/ml；P<0.001）、IL10（8.33（8.3）与 2.05（1.37）pg/ml；P=0.001）和 TNFα（6.14（8.95）与 3.61（3.58）pg/ml；P<0.001）在 WD 患者中也高于对照组。与无症状 WD 相比，神经 WD 患者的这些变化更为明显，与治疗患者相比，未治疗患者的变化更为明显。TAC 与疾病持续时间、血清游离铜、24 小时尿铜和血清铜蓝蛋白相关，谷氨酸与 MDA、TNFα、铜蓝蛋白和 24 小时尿铜相关。
在 WD 患者中，抗氧化剂减少，MDA、细胞因子和谷氨酸增加，在有症状的神经 WD 患者中比无症状患者更为明显。
