接上文 Part.1

Also, copper and zinc are regarded as neurotransmitters and are in high concentrations in brain hippocampus. As a result elevated copper and depressed zinc have been associated with hyperactivity, attention deficit disorders, behavior disorders, and depression. Also, many of those labeled with autism and paranoid schizophrenia have elevated blood copper levels in addition to other biochemical imbalances [1]. Elevated copper/zinc ratios can be especially serious for persons with low blood histamine. This combination of imbalances has been associated with anxiety, panic disorders, paranoia, and, in severe cases, hallucinations [1]. Low histamine patients are typically overstimulated with thoughts racing through their minds making normal ideation difficult. Low histamine children are hyperactive while often healthy in other respects. Serum Cu levels in these patients are abnormally high. Since Cu is a brain stimulant and destroys histamine (over-methylation), the elevated serum (and presumably brain) Cu level probably accounts for many symptoms, including the low blood histamine level. If the laboratory tests showed a high copper: low zinc ratio and low histamine levels, the treatment should consist of the administration of zinc, manganese, vitamin C, niacin, vitamin B-12, and folic acid. Folic acid in conjunction with B-12 injections raises blood histamine while lowering the degree of symptomatology. Zn allows for the normal storage of histamine in both the blood cells and the brain. Zn and Mn increase the urinary excretion of Cu [178].

此外，铜和锌被认为是神经递质，在大脑海马中浓度很高。因此，升高的铜和降低的锌与多动症、注意力缺陷障碍、行为障碍和抑郁症有关。此外，许多被标记为自闭症和偏执型精神分裂症的人除了其他生化失衡外，还具有升高的血铜水平 [1]。对于低血组胺的人来说，铜/锌比率升高可能特别严重。这种不平衡的组合与焦虑、恐慌症、妄想症有关，在严重的情况下还会出现幻觉 [1]。低组胺患者通常会被过度刺激的想法通过他们的思维进行正常构想困难。低组胺儿童多动，但在其他方面通常很健康。这些患者的血清铜水平异常高。由于铜是一种大脑兴奋剂并破坏组胺（过度甲基化），血清（可能是大脑）铜水平升高可能是许多症状的原因，包括血液组胺水平低。如果实验室测试显示高铜：低锌比率和低组胺水平，则治疗应包括给予锌、锰、维生素C、烟酸、维生素B-12和叶酸。叶酸与B-12注射剂结合可提高血液组胺，同时降低症状程度。锌允许组胺在血细胞和大脑中正常储存。锌和锰增加尿中铜的排泄 [178]。

On the other hand in the research of Effect of a deficiency of ceruloplasmin copper in blood plasma on copper metabolism in the adult rat brain, the copper deficiency in adult rats was induced by addition of silver chloride to the feed [179]. The concentrations of silver, copper, iron, and zinc and relative activity of genes for copper transporting proteins and copper enzymes were measured in the cortex, cerebellum, hippocampus, amygdala, pituitary gland, and hypothalamus. Silver was accumulated only in the hypothalamicpituitary system. These changes were accompanied by a decrease in the concentration of copper and increase in the contents of iron and zinc. Activity of genes for copper transport enzymes (high-affinity copper transporter; and two copper transport ATPases, ATP7A and ATP7B) and copper enzymes that were formed in the intracellular secretory pathway did not decrease in the brain of rats with copper deficiency. Relative activity of genes for intracellular copper enzymes (Cu/Zn superoxide dismutase and subunit IV of cytochrome c oxidase), concentration of immunoreactive polypeptides of superoxide dismutase, and enzymatic activity of superoxide dismutase remained unchanged under these conditions [179].

另一方面，在血浆中铜蓝蛋白缺乏对成年大鼠脑中铜代谢的影响的研究中，成年大鼠的铜缺乏是通过在饲料中添加氯化银引起的[179]。在皮质、小脑、海马、杏仁核、垂体和下丘脑中测量银、铜、铁和锌的浓度以及铜转运蛋白和铜酶基因的相对活性。银仅在下丘脑-垂体系统中积累。这些变化伴随着铜浓度的降低和铁和锌含量的增加。铜转运酶（高亲和力铜转运蛋白；和两种铜转运ATP酶，ATP7A和ATP7B）和在细胞内分泌途径中形成的铜酶的基因活性在缺铜大鼠的大脑中没有降低。在这些条件下，细胞内铜酶（铜/锌超氧化物歧化酶和细胞色素C氧化酶的亚基IV）基因的相对活性、超氧化物歧化酶的免疫反应性多肽浓度和超氧化物歧化酶的酶活性保持不变[179]。

Hippocampal neuronal injury: An experiment was conducted to investigate whether intracellular zinc depletion can actually change expression of voltage-dependent anion channel VDAC1 and VDAC2 in cultured hippocampal neurons of rats. Hippocampal neurons were obtained by primary culture from hippocampus of newborn rats. Cultured hippocampal neurons were exposed to a cell membrane permeable zinc chelator – ethylenediamine. The results demonstrated that exposure of hippocampal neurons to chelator for 24 hours induced notably neuronal injury, significantly increased the number of apoptotic nuclei, up-regulated the expression of VDAC1 protein level and down-regulated the expression of VDAC2 protein level. Significant down-regulation of mRNA levels for both, VDAC1 and VDAC2 were observed. Co-addition of zinc almost completely reversed chelator induced neuronal injury and above alterations in VDAC1 and VDAC2 protein levels and mRNA levels. Present results implicate a possibility that up-regulation of VDAC1 and down-regulation of VDAC2 may participate in hippocampal neuron injury induced by zinc deficiency [180].

海马神经元损伤：进行了一项实验，研究细胞内缺锌是否真的可以改变培养的大鼠海马神经元中电压依赖性阴离子通道VDAC1和VDAC2的表达。海马神经元通过原代培养从新生大鼠的海马中获得。培养的海马神经元暴露于细胞膜可渗透的锌螯合剂-乙二胺。结果表明，海马神经元暴露于螯合剂24小时可引起明显的神经元损伤，显著增加凋亡细胞核的数量，上调VDAC1蛋白水平的表达，下调VDAC2蛋白水平的表达。观察到VDAC1和VDAC2的mRNA水平显著下调。锌的共同添加几乎完全逆转了螯合剂诱导的神经元损伤以及VDAC1和VDAC2蛋白水平和mRNA水平的改变。目前的结果表明，VDAC1的上调和VDAC2的下调可能参与缺锌诱导的海马神经元损伤 [180]。

Traumatic brain injury: Depression, anxiety, and impairments in learning and memory are all associated with traumatic brain injury (TBI). Because of the strong link between zinc deficiency, depression, and anxiety, in both humans and rodent models, scientists hypothesized that dietary zinc supplementation prior to injury could provide behavioral resiliency to lessen the severity of these outcomes after TBI. Rats were fed with marginal zinc deficient, zinc adequate, or zinc supplemented diet for 4weeks followed by a moderatelysevere TBI. While moderate zinc deficiency did not worsen outcomes following TBI, rats that were fed with the zinc supplemented diet for 4weeks showed significantly attenuated increases in adrenal weight.(p<0.05) as well as reduced depression-like behaviors (p<0.001). Supplementation prior to injury improved resilience such that there was significant improvements in cognitive behavior compared to injured rats fed an adequate diet (p<0.01). These data suggest a role for supplemental zinc in preventing cognitive and behavioral deficits associated with TBI [181].

创伤性脑损伤：抑郁、焦虑以及学习和记忆障碍都与创伤性脑损伤 (TBI) 有关。由于在人类和啮齿动物模型中缺锌、抑郁和焦虑之间存在密切联系，科学家们假设在受伤前补充锌可以提供行为弹性以减轻TBI后这些结果的严重程度。给大鼠喂食边缘缺锌、锌充足或补锌的饮食4周，然后是中度严重的TBI。虽然中度缺锌不会使TBI后的结果恶化，但喂食4周补锌饮食的大鼠肾上腺重量的增加显著减弱（p<0.05）以及抑郁样行为减少 （p<0.001）。受伤前的补充提高了恢复力，因此与喂食充足饮食的受伤大鼠相比，认知行为有显著改善（p<0.01）。这些数据表明补充锌在预防与TBI相关的认知和行为缺陷方面的作用 [181]。

Brain ischemia: To determine whether the mitochondria or cytoplasm produces superoxides during ischemia - reperfusion of the brain, experts analyzed lucigenine-enhanced chemiluminescence emission in slices of mouse brain tissue prepared from manganesesuperoxide dismutase (MnSOD2)-deficient and copper/zincsuperoxide dismutase [Cu/ZnSOD1]-deficient mice during oxygenation and hypoxia-reoxygenation. The steady-state level of chemiluminescence under oxygenated conditions was significantly enhanced by a lack of either SOD. They hypothesized that the enhanced chemiluminescence produced by SOD2 and SOD1 deficiency reflects in situ superoxide generation in the mitochondria and cytoplasm, respectively. The study also indicated that the major site of intracellular superoxide generation in the brain during oxygenation is the cytoplasm, whereas it is the mitochondria during reoxygenation [182].

脑缺血：为了确定线粒体或细胞质是否在脑缺血再灌注期间产生超氧化物，专家分析了由锰超氧化物歧化酶（MnSOD2）缺乏和铜/锌超氧化物制备的小鼠脑组织切片中的光泽精增强的化学发光发射在氧合和缺氧复氧过程中歧化酶 [Cu/ZnSOD1] 缺陷小鼠。由于缺乏任何一种SOD，氧化条件下化学发光的稳态水平显著增强。他们假设SOD2和SOD1缺乏产生的增强化学发光分别反映了线粒体和细胞质中原位超氧化物的产生。该研究还表明，在氧合过程中，大脑中细胞内超氧化物产生的主要部位是细胞质，而在再氧合过程中则是线粒体 [182]。

Autism: Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents, such as glutathione, and other antioxidants involved in the defense system against reactive oxygen species. Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased in this disease. Levels of major antioxidant serum proteins, namely transferrin and ceruloplasmin are also decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously acquired language skills [183,184]. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper metabolism [185]. The membrane phospholipids, the prime target of reactive oxygen species, are also altered [186]. Several studies have suggested alterations in the Cu/ Zn ratio, the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase, altered glutathione levels and homocysteine/methionine metabolism in autism [183-187]. One study has hypothesized that there is a significant difference in the copper/zinc ratio between young children who have autism and their typically developing peers and trying to test the hypothesis could correction of elevated copper to zinc ratios in children with autism be accomplished by oral supplementation with zinc and vitamin C, and if these children show measurable changes in improvement in receptive or expressive language or behavioral parameters associated with autism after supplementations with some of trace elements. Anyway, the results about this research topic have not yet been revealed [188]. Additionally, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental and genetic factors may increase vulnerability to oxidative stress in autism [188].

自闭症：自闭症是一种严重的发育障碍，病因知之甚少。自闭症中的氧化应激已经在膜水平进行了研究，还通过测量脂质过氧化产物、解毒剂（如谷胱甘肽）和其他参与防御活性氧物质防御系统的抗氧化剂的产物进行了研究。自闭症患者的脂质过氧化标志物升高，表明这种疾病的氧化应激增加。自闭症儿童的主要抗氧化血清蛋白，即转铁蛋白和铜蓝蛋白水平也降低。这些蛋白质水平的降低与先前获得的语言技能的丧失之间存在正相关关系[183,184]。铜蓝蛋白和转铁蛋白水平的改变可能导致铁和铜代谢异常 [185]。膜磷脂，即活性氧的主要目标，也发生了改变[186]。几项研究表明，自闭症患者的铜/锌比率、抗氧化酶（如超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶）的活性会改变谷胱甘肽水平和同型半胱氨酸/蛋氨酸代谢 [183-187]。一项研究假设患有自闭症的幼儿与其正常发育的同龄人之间的铜/锌比率存在显著差异，并且试图验证该假设可以通过口服补充剂来纠正自闭症儿童的铜/锌比率升高与锌和维生素C，如果这些儿童在补充一些微量元素后在接受或表达语言或与自闭症相关的行为参数方面表现出可测量的变化。无论如何，关于这个研究课题的结果尚未公布[188]。此外，自闭症患者的炎症、兴奋性毒性以及线粒体和免疫功能障碍增加。此外，环境和遗传因素可能会增加自闭症患者对氧化应激的脆弱性[188]。

Amyotrophic lateral sclerosis: Amyotrophic lateral sclerosis disease (ALS) is a multifactor and multigenic disorder with still unknown aetiology and pathogenesis. The pathological characteristics of ALS include protein aggregation, proteasome inhibition, impaired axonal transport, mitochondria damage and apoptosis, oxidative stress, glutamate induced excitotoxicity, neuroinflammation and transcriptional dysfunction. Many compounds targeted to one or more of these mechanisms have been tested in multiple clinical trials. Nonetheless, nowadays only one drug, riluzole, has demonstrated a positive effect in the disease progression, but a number of recentcompounds are promising in ALS therapy [189]. The discovery that in approximately 10% of ALS patients mutations in SOD1 gene cause a subset of familial amyotrophic lateral sclerosis has attracted great attention, and studies have been mainly focused on discovering mutations in the coding region and investigation at protein level. Considering that changes in SOD1 mRNA levels have been associated with sporadic ALS, a molecular understanding of the processes involved in the regulation of SOD1 gene expression could unravel novel regulatory pathways that may govern cellular phenotypes and changes in diseases. The progress in understanding the mechanisms of transcriptional and post-transcriptional control could offer hope for the development of new-generation drugs or medical treatment strategies [190].

肌萎缩侧索硬化症：肌萎缩侧索硬化症(ALS)是一种多因素和多基因疾病，病因和发病机制尚不清楚。ALS的病理特征包括蛋白质聚集、蛋白酶体抑制、轴突运输受损、线粒体损伤和细胞凋亡、氧化应激、谷氨酸诱导的兴奋性毒性、神经炎症和转录功能障碍。许多针对这些机制中的一种或多种的化合物已在多项临床试验中进行了测试。尽管如此，现在只有一种药物利鲁唑在疾病进展中表现出积极作用，但最近的一些化合物ALS治疗中很有前景 [189]。大约10%的ALS患者SOD1基因突变导致家族性肌萎缩侧索硬化症的发现引起了极大的关注，研究主要集中在发现编码区的突变和蛋白质水平的研究。考虑到SOD1 mRNA水平的变化与散发性ALS相关，对SOD1基因表达调控过程的分子理解可以揭示可能控制细胞表型和疾病变化的新调控途径。了解转录和转录后控制机制的进展可以为开发新一代药物或医疗策略提供希望 [190]。

Because alteration of the activity of SOD1 leads to an oxidative stress imbalance, which damages the structure of lipids and proteins in the CNS, the membrane fluidity was monitored in the spinal cord and the brain in a widely used animal model of ALS, the SOD)(G93A) mouse, which develops symptoms similar to ALS with an accelerated course. The results show that the membrane fluidity of the spinal cord in this animal model significantly decreased in symptomatic animals compared with age-matched controls. Changes in membrane fluidity likely contribute substantially to alterations in cell membrane functions in the nervous tissue from SOD(G93A) mice [191]. Also, the spinal cord and brain of SOD(G93A) mice showed increased lipid peroxidation after 100 or 130 days compared to age-matched controls. The CNS was most affected, but lipid peroxidation was also detected in the skeletal muscle and liver on day 130. Thus, oxidative stress represents a potential biomarker that might be useful in developing new therapeutic strategies for ALS [192]. When replete with zinc and copper, amyotrophic lateral sclerosis (ALS)-associated mutant SOD proteins can protect motor neurons in culture from trophic factor deprivation as efficiently as wild-type SOD. However, the removal of zinc from either mutant or wild-type SOD results in apoptosis of motor neurons through a copper- and peroxynitrite-dependent mechanism. It has also been shown that motor neurons isolated from transgenic mice expressing mutant SODs survive well in culture but undergo apoptosis when exposed to nitric oxide via a Fas-dependent mechanism. It was found that zinc-deficient SOD-induced motor neuron death required Fas activation, whereas the nitric oxide-dependent death of SOD(G93A)-expressing motor neurons required copper and involved peroxynitrite formation. Surprisingly, motor neuron death doubled when Cu/Zn-SOD protein was either delivered intracellularly to SOD(G93A)-expressing motor neurons or co-delivered with zincdeficient SOD to nontransgenic motor neurons. These results could be rationalized by biophysical data showing that heterodimer formation of Cu/Zn-SOD with zinc-deficient SOD prevented the monomerization (the active form of the enzyme) and subsequent aggregation of zincdeficient SOD. Taken together, these results are consistent with coppercontaining zinc-deficient SOD being responsible for the toxic gain of function conferred by mutant SOD [193].

由于SOD1活性的改变会导致氧化应激失衡，从而破坏CNS中脂质和蛋白质的结构，因此在广泛使用的ALS动物模型（SOD）中监测脊髓和大脑中的膜流动性（G93A）小鼠，其症状与ALS相似，病程加快。结果表明，与年龄匹配的对照组相比，该动物模型中脊髓的膜流动性在有症状的动物中显著降低。膜流动性的变化可能对SOD（G93A）小鼠神经组织中细胞膜功能的改变有很大影响 [191]。此外，与年龄匹配的对照组相比，SOD（G93A）小鼠的脊髓和大脑在100或130天后显示出脂质过氧化增加。中枢神经系统受到的影响最大，但在第130天还在骨骼肌和肝脏中检测到脂质过氧化。因此，氧化应激是一种潜在的生物标志物，可能有助于开发新的ALS治疗策略 [192]。当富含锌和铜时，肌萎缩侧索硬化症（ALS）相关的突变SOD蛋白可以像野生型SOD一样有效地保护培养中的运动神经元免受营养因子剥夺。然而，从突变型或野生型SOD中去除锌会通过铜和过氧亚硝酸盐依赖性机制导致运动神经元凋亡。还表明，从表达突变SOD的转基因小鼠中分离出的运动神经元在培养中存活良好，但在通过Fas依赖性机制暴露于一氧化氮时会发生细胞凋亡发现缺锌SOD诱导的运动神经元死亡需要Fas激活，而表达SOD（G93A）的运动神经元的一氧化氮依赖性死亡需要铜并涉及过氧亚硝酸盐的形成。令人惊讶的是，当Cu/Zn-SOD蛋白被细胞内递送至表达SOD（G93A）的运动神经元或与缺锌的SOD共同递送至非转基因运动神经元时，运动神经元死亡增加了一倍。这些结果可以通过生物物理数据来解释，表明Cu/Zn-SOD与缺锌SOD的异二聚体形成阻止了单体化（酶的活性形式）和随后的缺锌SOD聚集。综上所述，这些结果与含铜、缺锌的SOD是导致突变SOD赋予功能毒性增加的原因一致 [193]。

Alzheimer’s disease: Alzheimer’s disease (AD) is a highly heterogeneous and progressive dementia which is characterised by a progressive decline in cognitive functioning, selective neuronal atrophy, and loss of cortical volume in areas involved in learning and memory. Recent study has indicated that the AD-affected brain is also besieged by increases in oxidative stress as well as perturbations to the homeostasis of biometals, such as copper and iron. These metals are known to interact with the neuropathological hallmark of AD, the β-amyloid peptide (Aβ), in a manner which increases Aβ's neurotoxic effects. The reported results suggest that zinc competes with copper for Aβ binding and inhibits copper-mediated Aβ redox chemistry [194].

阿尔茨海默病：阿尔茨海默病 (AD) 是一种高度异质性和进行性痴呆，其特征是认知功能进行性下降、选择性神经元萎缩和学习和记忆相关区域的皮质体积减少。最近的研究表明，受AD影响的大脑也受到氧化应激增加以及生物金属（如铜和铁）稳态扰动的困扰。已知这些金属会与AD的神经病理学标志物β-淀粉样肽（Aβ）相互作用，从而增加Aβ的神经毒性作用。报告的结果表明，锌与铜竞争Aβ结合并抑制铜介导的Aβ氧化还原化学 [194]。

In another study dyshomeostasis of extracellular zinc and copper has been implicated in β-amyloid aggregation, the major pathology associated with Alzheimer disease. Presenilin mediates the proteolytic cleavage of the β-amyloid precursor protein to release β-amyloid, and mutations in presenilin can cause familial Alzheimer disease. In the recent study there was tested, whether presenilin expression affects copper and zinc transport in murine embryonic fibroblasts from presenilin knock-out mice. They observed a marked decrease in saturable uptake of radiolabeled copper and zinc in several tissues, including brain. Copper/zinc superoxide dismutase activity was significantly decreased and copper chaperone of SOD1 levels was also decreased. These data indicate that presenilins are important for cellular copper and zinc turnover, influencing SOD1 activity, and having the potential to indirectly impact β-amyloid aggregation through metal ion clearance [195].

在另一项研究中，细胞外锌和铜的体内平衡失调与β-淀粉样蛋白聚集有关，这是与阿尔茨海默病相关的主要病理学。早老素介导β-淀粉样前体蛋白的蛋白水解切割以释放β-淀粉样蛋白，早老素的突变可导致家族性阿尔茨海默病。在最近的研究中，测试了早老素表达是否影响早老素敲除小鼠的小鼠胚胎成纤维细胞中铜和锌的转运。他们观察到包括大脑在内的几种组织中放射性标记的铜和锌的饱和摄取显著减少。铜/锌超氧化物歧化酶活性显著降低，SOD1的铜伴侣蛋白水平也降低。这些数据表明，早老素对细胞铜和锌的转换很重要，影响SOD1活性，并有可能通过金属离子清除间接影响β-淀粉样蛋白的聚集 [195]。

Despite the crucial role of redox active metals like copper and iron in central biological reactions, their elevated levels are involved in the pathogenesis of Alzheimer’s disease. Similarly reactive oxygen/nitrogen species (ROS/RNS) produced during normal metabolic activities, specifically oxidative phosphorylation of the cell, are scavenged by superoxide dismutase, catalase, but impaired metabolic pathways tend to generate elevated levels of these ROS/RNS. Alterations in trace elements as iron, copper, and zinc may intensify this process and contribute for the pathogenesis of Alzheimer's disease [196].

尽管铜和铁等氧化还原活性金属在中枢生物反应中起着至关重要的作用，但它们的升高水平与阿尔茨海默病的发病机制有关。类似地，在正常代谢活动期间产生的活性氧/氮物质 (ROS/RNS)，特别是细胞的氧化磷酸化，被超氧化物歧化酶、过氧化氢酶清除，但受损的代谢途径往往会产生水平升高的这些ROS/RNS。铁、铜和锌等微量元素的变化可能会加剧这一过程，并有助于阿尔茨海默病的发病机制[196]。

The aim of the present study was to evaluate the status of plasma essential trace elements magnesium, copper, zinc, iron and selenium concentrations and their some related antioxidant enzyme activities, erythrocyte glutathione peroxidase (GPX), superoxide dismutase, and catalase activities in patients with Alzheimer’s disease. Fifty patients with AD and fifty healthy control subjects were included in this study. Plasma Cu and Zn concentrations by atomic absorption spectrometry (AAS), plasma Mg and Fe concentrations by spectrophotometric methods and plasma Se concentrations by graphite furnace AAS were determined. Erythrocyte GPX, SOD and catalase activities were measured by spectrophotometric methods. Plasma Mg, Cu, Zn, Fe and Se levels and erythrocyte GPX, SOD and catalase activities were found to be significantly lower in patients with AD compared with controls. These results suggest that alterations in essential trace elements and their related enzymes may play a role in the etiopathogenesis of AD. Also, there is a defect in the antioxidant defense system, which may lead to oxidative damage in patients with AD. The changes in antioxidant enzyme activities may be secondary to the alterations in their cofactor concentrations [197].

本研究的目的是评估血浆必需微量元素镁、铜、锌、铁和硒的浓度及其相关的抗氧化酶活性、红细胞谷胱甘肽过氧化物酶 （GPX）、超氧化物歧化酶和过氧化氢酶活性。阿尔茨海默氏病。本研究包括50名AD患者和50名健康对照受试者。用原子吸收光谱法（AAS）测定血浆铜和锌浓度，用分光光度法测定血浆镁和铁浓度，用石墨炉AAS测定血浆硒浓度。通过分光光度法测量红细胞GPX、SOD和过氧化氢酶活性。与对照组相比，AD患者的血浆镁、铜、锌、铁和硒水平以及红细胞GPX、SOD和过氧化氢酶活性显著降低。这些结果表明，必需微量元素及其相关酶的改变可能在AD的发病机制中起作用。此外，抗氧化防御系统存在缺陷，可能导致AD患者出现氧化损伤。抗氧化酶活性的变化可能继发于其辅因子浓度的变化 [197]。

接下文 Part.3