精神分裂症及抑郁症患者红细胞超氧化物歧化酶活力分析

本文测定了７５例精神分裂症、１１例抑郁症病人及３５例健康对照者的红细胞超氧化物歧化酶（ＳＯＤ）活力。结果发现精神分裂症病人的ＳＯＤ活力显著高于对照组，而抑郁症患者与对照组之间无显著性差异。精神分裂症患者的ＳＯＤ活力与其ＢＰＲＳ总分及ＳＡＰＳ总分呈显著正相关关系，与病程、性别、年龄及ＳＡＮＳ总分无相关关系。     

Methamphetamine causes lipid peroxidation and an increase in superoxide dismutase activity in the rat striatum

The administration of methamphetamine to experimental animals results in damage to nigrostriatal dopaminergic neurons. In the present study, we demonstrated that both the acute repeated and the chronic administration of methamphetamine causes an increase in thiobarbituric acid reactive substances, which are indicators of lipid peroxidation, and superoxide dismutase activity in the rat striatum. The results of present study strengthen the notion that reactive oxygen species may play an important role in the methamphetamine-induced neurotoxicity.     

Attenuation of zinc-induced intracellular dysfunction and neurotoxicity by a synthetic superoxide dismutase/catalase mimetic,in cultured cortical neurons

Excessive extracellular zinc may contribute to neuronal cell death following ischemia and seizures, although the mechanisms mediating zinc-induced cell death remain largely unknown. In this study, we examined potential cellular and molecular mechanisms associated with zinc neurotoxicity and determined the neuroprotective effects of the superoxide dismutase (SOD)/catalase mimetic, EUK-134. Cortical neuron cultures exposed to zinc for 24 h exhibited concentration-dependent increases in lactate dehydrogenase (LDH) release and number of apoptotic cell bodies. Both effects were prevented by treatment with EUK-134. Zinc exposure resulted in increased release of cytochrome c from the mitochondria into the cytosol. Treatment with EUK-134 blocked this parameter of mitochondrial dysfunction. Exposure of cultures to zinc for 4 h produced an elevation of reactive oxygen species (ROS) as determined by increased 2,7-dichlorofluorescein (DCF) fluorescence, which was followed by an increase in lipid peroxidation. EUK-134 completely attenuated ROS production and subsequent oxidative damage. Finally, zinc exposure activated NF-κB, an effect also prevented by EUK-134. These data indicate that multiple cellular and molecular mechanisms are involved in zinc neurotoxicity. As all these mechanisms appear to be sensitive to treatment with EUK-134, our data suggest that oxidative stress occurs early in the cascade of events triggered by zinc.     

Orcadian variations of superoxide dismutase activity in the rat pineal gland

Summary The 24 h profile of the activity of the antioxidant enzyme Superoxide dismutase (SOD) in the pineal gland of rats was studied. Rhythmic analysis showed a significant 24 h rhythm with an amplitude of oscillation of 25% of the 24 h mean value, that was 100.34±1.6 U SOD (nitrite). An ultradian rhythm of 9 h was also detected. The diurnal profile of Superoxide dismutase activity is discussed in relation to the oxidative metabolism of the pineal gland.     

氟哌啶醇对精神分裂症超氧化物歧化酶的作用

目的：探讨精神分裂症自由基代谢酶超氧化物歧化酶（ＳＯＤ）在氟哌啶醇治疗前后的变化。方法：用固定剂量氟哌啶醇治疗４６例慢性精神分裂症患者１２周，在治疗前后应用放射免疫法测定血ＳＯＤ含量，并评定ＢＰＲＳ、ＳＡＰＳ和ＳＡＮＳ量表。结果：治疗前ＳＯＤ值与ＳＡＰＳ总分正相关（Ｐ〈０．０５）。治疗后，治疗前高ＳＯＤ组明显降低，而低ＳＯＤ组明显增高（Ｐ均〈０．０５）。阴性型亚组中，治疗前ＳＯＤ值与治疗前后ＳＡＮ     

Hydroxyl radical and superoxide dismutase in blood of patients with Parkinson's disease: relationship to clinical data

Hydroxyl radical (·OH) levels in blood, superoxide dismutase (SOD) activity in plasma (plasma-SOD) and in red blood cells (RBC) relative to Cu,Zn-SOD (SOD1) protein (RBC-SOD/SOD1), SOD1 protein in RBC (SOD1/RBC) and plasma (SOD1/plasma), and Mn-SOD protein in plasma (SOD2/plasma) were measured in patients with Parkinson’s disease (PD), multiple-system atrophy (MSA) with parkinsonism, and in control subjects. Patients with PD had significantly higher ·OH and plasma-SOD values and significantly lower RBC-SOD/SOD1 and SOD1/RBC values than the corresponding MSA and control values. In PD, RBC-SOD/SOD1 values were significantly lower in older patients and were negatively correlated with age. ·OH levels were significantly higher in PD patients with early onset, a long period of illness or severe Yahr stage, and were negatively correlated with onset and positively correlated with duration of illness. RBC-SOD/SOD1 values in PD patients who received pergolide therapy were significantly higher than those in PD patients who received neither pergolide nor bromocriptine therapy. Therefore, the higher ·OH level and the lower SOD1 activity may play a role in the onset and progression of PD, and pergolide may act neuroprotectively by inducing SOD1 activity.     

Increased activity of superoxide dismutase in kindled brain and suppression of kindled seizure following intra-amygdaloid injection of superoxide dismutase in rats

The possible role played by superoxide dismutase (SOD), a major defense system for counteracting the toxic effects of oxygen free radicals, in amygdaloid (AM) kindling was examined in rats. A significant increase of total SOD activity in the whole brain was observed 30 days after completion of AM kindling. Intra-AM injection of 3 ng of one of the 2 SOD enzymes present in mammalian brain, i.e. cytosolic SOD containing copper and zinc (CuZn-SOD) caused suppression of kindled seizure. These results suggest that SOD participates in the persistence of AM kindled seizure susceptibility and the initiation of kindled AM seizure.     

An immunohistochemical study of copper/zinc superoxide dismutase and manganese superoxide dismutase following focal cerebral ischemia in the rat

We investigated immunohistochemically the localization and changes of copper/zinc superoxide dismutase (CuZn-SOD) and manganese superoxide dismutase (Mn-SOD) in the rat brain following 1 h of middle cerebral artery (MCA) occlusion. In normal brain, immunoreactivity to both SODs was observed in medium-sized neurons in the striatum and in many neurons in the neocortex. Mn-SOD was predominantly stained in cortical interneurons. The immunostaining of both SODs rapidly decreased or disappeared in neurons in the lateral segment of the striatum (ischemic center) 4 h after MCA occlusion, when the neurons were degenerating. Most neurons in the neocortex (ischemic penumbra) decreased their CuZn-SOD immunoreactivity but not Mn-SOD immunoreactivity 4 h after ischemia, when only a few neurons showed histopathological changes. CuZn-SOD immunoreactivity in almost all cortical neurons disappeared 1 day after ischemia, but Mn-SOD immunoreactivity was still preserved in interneurons, when cortical neurons showed typical pathological changes. Some cortical neurons in the boundary zone between normal and infarcted areas showed intense immunostaining to both SODs and glial SOD immunoreactivity appeared after 3 and 7 days. These results suggest that early loss of the scavenging system of free radicals may lead to neuronal damage after ischemic insult, and that induced SODs in the boundary zone between the normal and infarcted areas may act as a defense mechanism against damage.     

(−)-Deprenyl can induce soluble superoxide dismutase in rat striata

Summary (–)-Deprenyl (0.25 or 2mg/kg) or saline was injected daily into male Wistar rats for 3 weeks. The striata were dissected out and soluble and particulate Superoxide dismutase activity measured. (–)-Deprenyl at 2mg/kg induced a significant increase in the soluble but not the particulate form of the enzyme. The possibility that this action contributes to the ability of (–)-deprenyl to retard nigral degeneration in man and prolong life in rats is discussed.     

美解眠诱发癫痫大鼠大脑皮质NO和SOD的变化研究

目的：观察癫痫大鼠脑中的一氧化氮（NO）和超氧化物歧化酶（SOD）的变化,并探讨NO的氧化还原状态对癫痫的作用。方法：通过美解眠诱发致痫的大鼠模型,分别取癫痫发作时及癫痫发作刚停止时的大脑运动区皮质,匀浆后测定NO的含量和SOD活力。结果：癫痫发作组及癫痫发作刚停止组,大脑运动皮质的NO含量均较正常对照组明显升高;癫痫发作组,脑内SOD活力反而下降,癫痫发作刚停止组,脑内SOD活性力明显升高,结论：癫痫发作组和短暂发作刚停止组,SOD活力／NO含量比值具有显著差异,这些结果支持NO的不同氧化还原状态在癫痫发作中起到不同的作用。     

Impaired blood superoxide dismutase in the traumatic paraplegic patients

Blood superoxide dismutase (SOD) activity and blood copper, zinc-superoxide dismutase (Cu.Zn-SOD) content were measured by luminol chemiluminescence assay and by single radial immunodiffusion assay, respectively, in 50 patients with paraplegia due to traumatic injury to the spinal cord by the Tangshan Earthquake on July 28, 1976, compared with 20 age-matched healthy subjects. We found that blood SOD activity and blood Cu.Zn-SOD content in the paraplegic patients were significantly lower than those in healthy subjects (p < 0.01). In healthy subjects, blood Cu.Zn-SOD fully expressed the enzymatic activity, whereas only 77% of blood Cu.Zn-SOD in the paraplegic patients expressed the enzymatic activity, indicating that in the patients, part of blood Cu.Zn-SOD protein is in a state without function. Also the serum lipid peroxide level in the paraplegic patients was higher than that in healthy subjects (p < 0.05). These findings suggest decreased endogenous blood protection against oxygen derived free radicals in these paraplegic patients.     

Regional brain superoxide dismutase activity is altered differently by heat in warm and cool mice

The significant regional variation in brain superoxide dismutase (SOD) activity was similar in mice from both warm and cool cohorts. Mice in the cool cohort generally had higher SOD activity, which varied significantly with body temperature in striatum and in preoptic area of the hypothalamus. Changes in SOD activity following heating were revealed only when warm and cool cohorts were analysed separately. SOD activity decreased significantly in striatum, hypothalamus, and hippocampus of the cool cohort only. The decline was to levels consistent with those of the warm cohort. Body temperature of cool mice increased more than that of warm mice following each increment of heating so resultant body temperatures became similar. The role of SOD as part of a differential defense against heat stress in warm and cool mice is presented.     

Distribution of mitochondrial manganese superoxide dismutase among rat glial cells in culture

Enzymatic antioxidant defense systems, like superoxide dismutase (SOD), may protect neuronal and glial cells from reactive oxygen species (ROS) damage. Beside the cytosolic constitutive CuZn SOD, mitochondrial manganese SOD (Mn SOD) represents a ROS inducible enzyme which should allow the adaptation of brain cells to variation in ROS concentrations resulting from their oxidative metabolism. Using immunocytochemistry, the distribution of Mn SOD among the various representatives of the rat brain glial population (astroglia and microglia in primary culture as well as oligodendroglia in secondary culture) has been examined. Among astroglial cells, only a population of flat polygonal-shaped astrocytes, highly immunostained for glial fibrillary acid protein (GFAP) express Mn SOD immunoreactivity. Microglial cells defined by their shape and OX-42 immunoreactivity also express an intense Mn SOD signal. Exposure of the primary culture to reactive oxygen species generated by a xanthine/xanthine oxidase mixture (X/XO) accentuates the Mn SOD signal in astroglial and microglial cells. On the contrary, oligodendroglial cells grown in secondary culture in a serum-free chemically defined or a serum-containing medium and well characterized by their 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) immunoreactivity never express any immunostaining for Mn SOD, even in response to an extracellular reactive oxygen species generating source like X/XO. Likewise, a population of A2B5-positive glial cells which may represent bipotential O-2A progenitor precursors does not express Mn SOD immunostaining. These results point out that in addition to the well known ability of microglial and astroglial cells to secrete ROS, they also express a high mitochondrial oxygen superoxide decomposition potential. On the contrary, the absence of any observable Mn SOD signal in precursors and in more differentiated oligodendroglial cells could be related to their great sensitivity to ROS damage and could therefore play an important role in the development of various dysmyelinating disorders. GLIA 22:408–414, 1998. © 1998 Wiley-Liss, Inc.     

中国家族性肌萎缩侧索硬化患者超氧化物歧化酶1基因突变分析

目的 肌萎缩侧索硬化(ALS)是上、下运动神经元退变引起的一种进行性致死性疾病,家族性ALS占10%～20%,铜锌SOD1基因突变存在于20%的家族性患者和少数散发性患者,某些突变还具有地域分布和特殊临床表型的规律性.我们旨在分析我国3个家族性ALS家系SOD1基因突变特点,并与不同国家和地区SOD1突变比较,分析其临床表型的特征性.方法 提取患者外周血基因组DNA,采用SOD1基因的5对引物对其5个外显子进行PCR扩增,产物直接测序.归纳整理患者临床表型资料,进行表型-基因型关联分析.结果 家系1中SOD1基因外显子2的H46R杂合突变,即CAT→CGT,使得46位由编码组氨酸变为编码精氨酸.先证者48岁,女性,43岁起病,主要表现为肢体无力和萎缩.家系中其他3例患者首发症状与先证者相似,病情进展均较缓慢,生存期较长.家系2中先证者20岁,男性,临床表现为延髓性麻痹,病程进展快速,生存期1年,位于3号外显子的杂合突变,即G72C突变.其父亲也出现同样的突变,但无ALS临床表现,其姑姑也有类似病史.家系3中5例患者5号外显子的E133V杂合突变,先证者中年起病,病程逐渐进展,生存期5年.结论 H46R的杂合突变国内未见报道,国外日本人曾多次报道及巴基斯坦有1个家系报道,欧美均未见报道,推测此突变可能为亚裔所特有.G72C突变的家系,临床表型为较早发病,病程进展迅速,生存期1年,突变外显率低导致家族成员不发病,常被诊断为散发病例,因此对于散发性患者及其家族成员同时检测SOD1基因突变十分必要.E133V突变的家系为国际首先报道.     

Polychlorinated biphenyl mixture aroclor 1254-induced oxidative stress plays a role in dopaminergic cell injury

Oxidative stress (OS) is thought to participate in the pathogenesis of neurodegenerative disorders, including Parkinson's disease (PD). Excessive reactive oxygen species (ROS) production can occur during the normal aging process or following exposure to environmental toxicants. Dopamine neurons, which degenerate during PD, are particularly sensitive to oxidative stress. Polychlorinated biphenyls (PCBs), persistent and widespread pollutants, have been shown to adversely impact dopaminergic (DAergic) pathways, but the role ROS play in neurotoxicity remains unclear. To test the hypothesis that PCB exposure compromises dopamine neurons by stimulating ROS production, the direct toxicity and oxidative stress response following PCB exposure was examined both in MN9D dopamine cells and primary mesencephalic cultures. PCBs induced a time- and concentration-dependent increase in ROS production, which preceded cytotoxicity. Whereas intracellular GSH depletion exacerbated PCB effects, antioxidant pretreatment attenuated ROS production and cell death. Coincident alterations in antioxidant defense enzymes also accompanied ROS production, including decreased MnSOD and increased CuZnSOD protein levels. The robust elevation in heme oxygenase-1 levels further support the activation of oxidative stress mechanisms following PCB exposure. Furthermore, PCBs produced concentration-dependent reductions in intracellular dopamine levels and elevated dopamine turnover. Although the intracellular source of ROS remains unknown, these results suggest that sublethal PCB concentrations activate an oxidative stress-related pathway, which potentially disrupts dopamine neuron function.     

精神分裂症、情感性精神障碍患者血超氧化物歧化酶的研究

目的探讨精神分裂症、情感性精神障碍患者血超氧化物歧化酶(SOD)含量与精神疾病的相关意义.方法采用放射免疫法测定130例精神分裂症患者、58例情感性精神障碍患者及50名健康人(对照组)的血SOD含量(ng/mg血红蛋白),并对其中64例精神分裂症患者经12周治疗后再次测定SOD;同时用简明精神病评定量表(BPRS)、汉密尔顿抑郁量表(HAMD)和Bech-Rafaelson躁狂量表(BRMS)分别对患者进行评定.结果精神分裂症、躁狂症患者的血SOD含量分别为1077±420、1044±292,均明显高于对照组(579±237),P＜0.01.抑郁症组SOD含量为701±267,与对照组的差异无显著性,P＞0.05;精神分裂症病程＜5年患者的SOD含量(1105±451)与≥5年组SOD含量(1035±346)的差异无显著性(P＞0.05);64例精神分裂症患者经12周治疗后的血SOD含量(627±217)低于治疗前(1009±364),P＜0.01.结论血SOD含量的增高也许能够反映精神疾病的存在,但不能有效区别是何种精神疾病.     

石杉碱甲治疗阿尔茨海默病SOD、LPO浓度变化

目的：用石杉碱甲胶丸治疗阿尔茨海默病（ＡＤ）,观察其红细胞和血浆内超氧化物歧化酶（ＳＯＤ）、过氧化脂质（ＬＰＯ）浓度变化与药物疗效之关系。方法：门诊患者３０例,每日服石杉碱甲胶丸共２月,于疗前、疗后１月、２月分别测定认知功能水平及红细胞和血浆内ＳＯＤ、ＬＰＯ浓度。结果：该药有效率达６３．３３％,能一定程序的改善记忆障碍和痴呆症状,治疗１、２个月后,红细胞和血浆内ＳＯＤ、ＬＰＯ浓度都较疗前有明显改善     

Changes in lipid peroxidation, Cu/Zn-superoxide dismutase and its mRNA following an intracerebroventricular injection of 6-hydroxydopamine in mice

A single i.c.v. injection of 6-hydroxydopamine (6-OHDA) in mice resulted in a biphasic increase in lipid peroxidation as assayed by the level of thiobarbituric acid-reacting substances (TBARS). An increase in Cu/Zn-superoxide dismutase (SOD) activity was temporally related with the first peak of TBARS but remained unchanged during the second TBARS peak. This suggests that a free radical species other than O₂⁻ may be involved in the late onset increase in TBARS. The level of Cu/Zn-SOD mRNA did not immediately reflect the change in Cu/Zn-SOD activity but rather increased gradually reaching significantly higher levels only 8 weeks after i.c.v. an injection of 6-OHDA. This increase in Cu/Zn-SOD mRNA likely occurs in response to a consumption of intrinsic SOD. Thus, short- and long-term increases in lipid peroxidation likely occur by different mechanisms and studies of both are needed to elucidate the neurodegenerative process.     

L-deprenyl potentiates NGF-induced changes in superoxide dismutase mRNA in PC12 cells

L-deprenyl protects neurons in a number of in vivo and in vitro models and it has been postulated that it ameliorates some neurodegenerative disorders. Superoxide dismutase (SOD) is one of the enzymes responsible for the inactivation of oxygen free radicals, and one of the mechanisms of the effect of L-deprenyl is thought to act by induction of SOD. In this study, PC12 cells were used to study the effect of L-deprenyl on gene regulation of SOD and its interaction with nerve growth factor (NGF). The results show that NGF induces SOD mRNA in a dose-dependent manner and that a similar effect was produced by L-deprenyl . In addition, L-deprenyl potentiates NGF effects. This study demonstrates that both L-deprenyl and NGF may be involved in common antioxidative mechanisms and that L-deprenyl may interact with neurotrophic factors. J. Neurosci. Res. 53:235–238, 1998. © 1998 Wiley-Liss, Inc.     

Overexpression of superoxide dismutase and catalase in immortalized neural cells: toxic effects of hydrogen peroxide

Hydrogen peroxide (H₂O₂) is a known toxicant which causes its damage via the production of hydroxyl radicals. It has been reported to cause both necrotic and apoptotic cell death. The present study was undertaken to evaluate the mode of H₂O₂-induced cell death and to assess if overexpression of catalase could protect against its toxicity. H₂O₂ causes cell death of immortalized CSM 14.1 neural cells in a dose-dependent manner. H₂O₂-induced death was associated with DNA laddering as shown by agarose gel electrophoresis. Stable overexpression of catalase by transfection of a vector containing human cDNA into these cells markedly attenuated H₂O₂-induced toxic effects. Transfection of a vector containing a SOD cDNA afforded no protection. These results indicate that H₂O₂ can lead to the activation of endonuclease enzyme that breaks DNA into oligosomes. These cells which overexpress catalase or SOD will help to determine the specific role of H₂O₂ or O₂^−. in the deleterious effects of a number of toxins.