Effects of Longyanshen polysaccharides on free radical metabolism in senescence accelerated-prone mice

BACKGROUND： Along with aging, antioxidase activity decreases and oxygen-derived free radicals greatly accumulate, resulting in cellular senescence, or even cell death. This is manifested by hypomnesia and disordered metabolism of free radicals. Studies have reported that Longyanshen polysaccharides have the function of antioxidation and improved brain memory. OBJECTIVE： To observe the effects of Longyanshen polysaccharides on free radical metabolism in brain tissue to verify the anti-aging mechanisms in senescence accelerated-prone （SAMP8） mice. DESIGN, TIME AND SETTING： The randomized, controlled, biochemical experiment was performed in the Department of Pharmacology and Scientific Experimental Center of Guangxi Medical University （China） from September 2005 to January 2008. MATERIALS： Forty SAMP8 mice were randomized into four groups： SAMP8 control group, as well as low-, mid-, and high-dose polysaccharide, with 10 mice in each group. Ten senescence accelerated-resistantprone （SAMR 1） mice served as the normal control group. Longyanshen polysaccharides, extracted from the medical plant Longyanshen, were supplied by the Department of Pharmacology, Guangxi Medical University Superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px）, malonaldehyde （MDA）, nitric oxide （NO）, and total protein test kitwere purchased from Nanjing Jiancheng Bioengineering Institute （China）. METHODS： SAMP8 mice were used to establish a dementia animal model. SAMP8 and SAMR1 control mice were administered 30 mL/kg saline. The low-, middle-, and high-dose polysaccharide groups were administered 45, 90, and 180 mg/kg Longyanshen polysaccharides, respectively. Each group was treated by intragastric administration, once daily, for 50 continuous days. MAIN OUTCOME MEASURES： One hour after the last administration, mouse brain tissues were collected, and retro orbital blood sampling was performed. Spectrophotometry was used to measure SOD and GSH-Px activity, as well as MDA and NO concentration in     

应激对D—半乳糖诱导的衰老小鼠海马线粒体膜流动性的影响

研究适当应激对衰老小鼠海马线粒体膜流动性的影响。Ｄ－半乳糖诱导的衰老小鼠同时进行游泳应激训练（１８℃,１５ｍｉｎ）,连续６周后,以ＤＰＨ为荧光探针,检测小鼠海马线粒体膜粘滞系数,同时测定线粒体丙二醛含量的变化。衰老组小鼠海马线粒体膜流动性降低,ＭＤＡ生成增加,而１８℃水温下的游泳训练能使衰老时线粒体中的ＭＤＡ含量减少,膜流动性增加。适当的应激可能通过减轻自由基的损害而增加衰老小鼠海马线粒体膜的流动性。     

莪术提取物对单纯疱疹病毒性脑炎模型小鼠脑血流动力学及氧化应激的作用

目的 探讨莪术提取物对单纯疱疹病毒性脑炎(Herpes simplex encephalitis, HSE)模型小鼠脑血流动力学及氧化应激的影响及其可能作用机制。方法 选取48只C57BL/6雄性小鼠脑部注射Ⅰ型单纯疱疹病毒建立HSE小鼠模型,造模成功小鼠随机分为模型组、莪术提取物低、高剂量(50、100 mg/kg)组、西药组(150 mg/kg阿昔洛韦)各12只,另设对照组12只;实验期间记录小鼠一般情况和存活天数并计算生命延长率;酶联免疫吸附法(Enzyme linked immunosorbent assay, ELISA)检测小鼠血清丙二醛(Malondialdehyde, MDA)、谷胱甘肽过氧化物酶(Glutathione peroxidase, GSH-Px)、超氧化物岐化酶(Superoxide dismutase, SOD)水平;激光散斑成像系统检测小鼠脑血流变化;苏木精-伊红染色法(Hematoxylin eosin staining, HE)染色观察小鼠脑组织病理学变化;实时荧光定量聚合酶链反应法(Real time fluorescent quantitati...     

抗氧化酶类对大鼠感染性脑损伤的内源性防护作用

目的 通过测定脑组织丙二醛（ＭＤＡ）、超氧化物歧化酶（ＣｕＺｎ－ＳＯＤ和Ｍｎ－ＳＯＤ）、过氧化氢酶（ＣＡＴ）及谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）活性的变化,探讨抗氧化酶类在大鼠感染性脑损伤内生防护机制听作用。方法 向大鼠左颈内动脉注射百日咳菌悬浮液,诱发感染性脑损伤模型。４０只大鼠随机分为生理盐水对照组（ＮＳ）和右日咳杆菌悬浮液组（ＢＰＳ）,观察时间为４ｈ和２４ｈ。用可见光和紫外分光光度法分别测定     

银杏叶提取物对衰老小鼠脑组织Klotho蛋白表达的影响及机制

目的观察银杏叶提取物(Ginkgo biloba extract,GBE)对D半-乳糖(D-gal)致衰老小鼠氧化系统指标及Klotho(KL)蛋白表达的影响,探讨GBE延缓衰老的机制。方法48只昆明雄性小鼠随机分为正常对照组、D-gal模型组、GBE组和D-gal联合GBE组。各组用相应药物连续处理6w。用比色法检测小鼠海马组织MDA和SOD的含量。免疫组织化学染色和Western blot检测小鼠脑脉络丛KL蛋白表达水平。结果与正常对照组比较,D-gal模型组小鼠脑脉络丛KL蛋白表达明显下降(P<0.01),MDA含量增高并且SOD活性降低(P<0.01),而用GBE可以显著逆转上述变化(P<0.01)。结论D-gal可下调小鼠脑脉络丛KL蛋白的表达。GBE可提高D-gal所致衰老小鼠的抗氧化活性及上调KL蛋白表达,发挥延缓衰老的作用。     

八角茴香提取液的抗疲劳效应*

背景：延缓疲劳或消除疲劳是运动医学的研究热点,利用中药来消除运动性疲劳,提高机体运动能力,具有重要应用前景。 目的：观察八角茴香提取液对小鼠的抗疲劳作用。 方法：将120只雄性昆明种小鼠按体质量随机分为4组：分别给予21,42,84 mL/(kg•d)的八角茴香提取液和蒸馏水, 35 d后,检测小鼠力竭游泳时间、爬杆时间及运动后血乳酸水平;40 d后,检测小鼠运动后肝糖原含量、血清尿素氮和乳酸脱氢酶活力。 结果与结论：八角茴香提取液可增加小鼠力竭游泳时间、爬杆时间及运动后肝糖原含量,提高运动后小鼠血乳酸脱氢酶活力,同时降低小鼠运动后血乳酸及尿素氮水平,尤以84 mL/(kg•d)八角茴香提取液的效果最明显(P < 0.05或P < 0.01)。说明八角茴香提取液有明显的抗疲劳作用。     

地黄多糖调控环状RNA0010729/miR-326通路对海马神经元缺氧复氧损伤的影响

目的 探讨地黄多糖对海马神经元缺氧复氧损伤的影响及其保护机制是否与调控环状RNA 0010729(circ_0010729)和微小RNA-326(microRNA-326,miR-326)表达有关。方法 体外培养大鼠海马神经元建立缺氧复氧损伤模型; 将大鼠海马神经元分为对照组、模型组、模型+地黄多糖低剂量组、模型+地黄多糖中剂量组、模型+地黄多糖高剂量组、模型+小干扰RNA阴性对照(Small interfering RNA negative control,si-NC)组、模型+si-circ_0010729组、模型+地黄多糖高剂量+空载质粒(Empty plasmid,pcDNA)组、模型+地黄多糖高剂量+pcDNA-circ_0010729组; 流式细胞术检测细胞凋亡; 试剂盒检测丙二醛(Malonaldehyde,MDA)水平和超氧化物歧化酶(Superoxide dismutase,SOD)活性; 实时定量聚合酶链式反应(Polymerase chain reaction,PCR)检测circ_0010729,miR-326表达水平; 荧光素酶报告实验确定circ_0010729和miR-326靶向关系。结果 与对照组比较,模型组细胞凋亡率、MDA水平、circ_0010729表达水平升高(P<0.05),SOD活性、miR-326表达水平降低(P<0.05); 与模型组比较,模型+地黄多糖低剂量组、模型+地黄多糖中剂量组、模型+地黄多糖高剂量组细胞凋亡率、MDA水平、circ_0010729表达水平降低(P<0.05),SOD活性、miR-326表达水平升高(P<0.05); 与模型+si-NC组比较,模型+si-circ_0010729组细胞凋亡率、MDA水平降低(P<0.05),SOD活性升高(P<0.05); 与模型+地黄多糖高剂量+pcDNA组比较,模型+地黄多糖高剂量+pcDNA-circ_0010729组细胞凋亡率、MDA水平升高(P<0.05),SOD活性降低(P<0.05)。结论 地黄多糖能够有效抑制缺氧复氧诱导的大鼠海马神经元凋亡和氧化损伤,其机制可能与抑制circ_0010729/miR-326通路有关。     

白灵菇真菌多糖对衰老模型小鼠学习记忆能力、脑组织超氧化物歧化酶活性和丙二醛含量的影响

目的探讨白灵菇真菌多糖对衰老模型小鼠学习记忆能力、脑组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量的影响。方法 72只健康成年ICR小鼠随机分为白灵菇真菌多糖低、中、高剂量组和脑复康治疗组、衰老小鼠模型组、正常对照组,每组12只小鼠。采用D-半乳糖注射法制作衰老小鼠模型。白灵菇真菌多糖低、中、高剂量组于制模第3周起每日分别给予白灵菇真菌多糖2 g/kg、3 g/kg、6 g/kg灌胃治疗,连续3周。脑复康治疗组同期给予脑复康620 mg/kg灌胃治疗,衰老小鼠模型组和正常对照组小鼠给予等量双蒸水替代。分别采用Y迷宫、黄嘌呤氧化酶法和TBA比色法检测各组小鼠学习记忆能力、脑组织SOD活性和MDA含量。结果衰老小鼠模型组学习记忆能力检测达标所需的训练次数明显多于正常对照组、脑复康治疗组、白灵菇真菌多糖中剂量和高剂量组(均P<0.05);而与白灵菇真菌多糖低剂量组比较差异无统计学意义。与衰老小鼠模型组比较,正常对照组、脑复康治疗组和白灵菇真菌多糖中、高剂量组小鼠脑组织SOD活性明显增强、MDA含量明显减少(P<0.05～0.01)。白灵菇真菌多糖低剂量组小鼠脑组织SOD活性、MDA含量与衰老小鼠模型组差异无统计学意义。结论中、高剂量白灵菇真菌多糖可改善D-半乳糖致衰老模型小鼠的学习记忆能力,这可能与其抗氧化作用有关。     

缺血后处理对糖尿病大鼠局灶性脑缺血再灌注损伤线粒体的影响

目的观察缺血后处理(I-Post)对糖尿病大鼠局灶性脑缺血再灌注损伤线粒体超微结构和功能的影响,探讨I-Post诱导的脑保护的可能机制。方法采用链脲佐菌(STZ)腹腔注射建立糖尿病大鼠模型,在此基础上通过线栓法建立大鼠大脑中动脉阻塞/再灌注模型。SD糖尿病大鼠随机分为4组(n=10),空白对照组、假手术组、缺血再灌注组(I/R组)、缺血后处理组(I-Post组)。于缺血90min再灌注6h后电镜下观察线粒体超微结构、测定缺血侧脑组织线粒体中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、Na+/K+-ATPase和Ca2+-ATPase活性。结果缺血后处理能明显减轻I/R引起的线粒体超微结构的损伤,提高线粒体SOD、GSH-Px、Na+/K+-ATPase和Ca2+-ATPase的活性(P<0.05或0.0),降低MDA的含量(P<0.05)。结论线粒体可能在I-Post诱导的脑保护中起关键性作用,I-Post诱导的脑保护机制可能与SOD、Na+/K+-ATP酶、Ca2+-ATP酶和GSH-Px活性增加有关。     

Mailuoning suppresses H2O2-induced cortical neuronal injury and correlates with increased catalase activity and inhibited oxidative stress function

BACKGROUND:Mailuoning, a Chinese herb, has been widely used in China to treat acute ischemic stroke, and the major component exhibits anti-oxidative effects. However, the precise anti-oxidation pathway remains uncertain.OBJECTIVE:To validate the protective effects of Mailuoning on H202-induced primary cortical neuron injury in embryonic mice.DESIGN, TIME AND SETTING:Comparative observation and in v#ro experiments were performed at the Jiangsu Key Laboratory for Molecular Medicine from January 2008 to September 2009.MATERIALS:Mailuoning (Nanjing Jinling Medical Company, China), reactive oxygen species (ROS) kit (Beyotime Biotechnology, China), superoxide dismutase (SOD), Cu/Zn SOD kit, malondialdehyde (MDA) kits (Nanjing Jiancheng, China), mitochondrial membrane potential (GMS10013.1, GENMED, USA) and catalase activity assay kit (Beyotime Biotechnology, China) were utilized for the present study.METHODS:Mouse embryonic cortical neurons were isolated and cultured with culture medium containing H2O2 (80 μmol/L) and/or Mailuoning (1.25 μg/mL) for 24 hours.MAIN OUTCOME MEASURES:Neuronal viability and death were detected by methyl thiazolyl tetrazdium and flow cytometry; ROS production was determined by flow cytometry; mitochondriai membrane potential was detected using fluorescent staining; SOD activity was detected using a modified nitroblue tetrazolium method; Cu/Zn SOD and catalase activity was detected by spectrophotometry; and MDA was determined using the lipid peroxidation method.RESULTS:H2O2 increased ROS production and MDA concentration (P < 0.05), and decreased mitochondrial membrane potential, SOD, Cu/Zn SOD and catalase activity (P < 0.05); the number of surviving neurons (P < 0.05) was also reduced. Mai/uoning reversed these changes.CONCLUSION:Mailuoning protects H2O2-induced injury in cortical cells by inhibiting ROS and MDA, increasing depolarization of mitochondrial membrane, and enhancing SOD and catalase activity.     

缺氧对小鼠离体脑线粒体氧化应激的影响

目的:探讨缺氧对小鼠离体脑线粒体氧化应激的影响.方法:SPF级雄性C57BL/6 小鼠24只,取脑制备线粒体悬液后,随机分成2组(每组12份).缺氧组:线粒体悬液中通入100%N 2和氧清除剂Na2S2O4 0.5 mmol稬-1致PO2测不到;常氧组:线粒体悬液置于空气中.37℃孵育30 min后观察线粒体超微结构并检测超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽(GSH)含量.结果:与常氧组比较,缺氧组线粒体超微结构严重损伤,SOD和GSH减少( P<0.01),MDA增加(P<0.01).结论:缺氧可致小鼠脑线粒体氧化应激损伤.     

枸杞多糖对小鼠脑缺血再灌注损伤的保护作用及其抗氧化应激的机制研究

目的探讨枸杞多糖(lycium barbarum polysaccharides,LBP)对缺血再灌脑损伤小鼠的保护作用及其可能的机制。方法通过颈总动脉栓线造成大脑中动脉缺血,缺血2 h后将栓线拔出以实现大脑中动脉血流再灌注,形成小鼠短暂性大脑中动脉阻塞(transient middle cerebral artery occlusion,t MCAO)模型,观察LBP(25 mg/kg,50 mg/kg和100 mg/kg)对小鼠脑梗死范围,脑含水量,神经症状的影响,采用Westernblot法检测缺血大脑皮质NOX4蛋白的表达,采用DHE染色法检测脑组织中ROS的生成,采用分光光度计检测缺血侧脑组织匀浆SOD活力,GSH-Px活力,及MDA含量。结果 LBP对缺血再灌注小鼠神经症状有明显的改善作用,能明显降低脑梗死范围和脑含水量。Westernblot结果显示:小鼠缺血再灌后,缺血侧大脑皮质NOX4蛋白水平明显增高,LBP能显著降低NOX4蛋白水平。DHE染色显示,LBP能显著降低缺血再灌后ROS的生成。LBP能升高SOD和GSH-Px活力,降低MDA含量。结论 LBP对缺血再灌注小鼠脑损伤有明显保护作用,该作用可能与其抑制脑缺血再灌注引起的氧化应激损伤有关。     

Antioxidant enzyme and malondialdehyde levels in patients with social phobia

A growing body of reports have indicated that free radicals are involved in the etiopathogenesis of some neuropsychiatric disorders. In the present study, we aimed to evaluate whether antioxidant enzymes (superoxide dismutase; SOD, glutathione peroxidase; GSH-Px, and catalase; CAT) activity levels and malondialdehyde (MDA), a product of lipid peroxidation, were associated with social phobia (SP). Eighteen patients diagnosed with SP and 18 healthy controls were enrolled. A clinical evaluation and measurements of MDA, SOD, GSH-Px and CAT were performed. Additionally, all patients were assessed with the Liebowitz Social Anxiety Scale (LSAC). The mean MDA, SOD, GSH-Px and CAT levels in the patient group were significantly higher than those in the control group. There was a positive correlation between LSAC scores and MDA, SOD, GSH-Px and LSAC levels, and between the duration of illness, and MDA, SOD and CAT levels in the patient group. In conclusion, our results suggest that there may be a relationship between increased antioxidant enzyme levels and MDA, and SP.     

Prophylactic neuroprotective property of Centella asiatica against 3-nitropropionic acid induced oxidative stress and mitochondrial dysfunctions in brain regions of prepubertal mice

Despite the increasing popularity of Centella asiatica (a well known plant in ayurvedic medicine) globally, evidence demonstrating its protective efficacy against neurotoxicants in animal models is limited. 3-Nitropropionic acid (3-NPA), a fungal toxin is a well known neurotoxicant which induces selective striatal pathology similar to that seen in Huntington's disease. The present study aimed to understand the neuroprotective efficacy of a standardized aqueous extract of C. asiatica (CA) against 3-NPA-induced early oxidative stress and mitochondrial dysfunctions in striatum and other brain regions. We determined the extent of oxidative stress in cytosol and mitochondria of brain regions of male mice (4 wk old) given CA prophylaxis (5 mg/kg bw) for 10 days followed by 3-NPA administration (i.p., 75 mg/kg bw/d) on the last 2 days. The neurotoxicant elicited marked oxidative stress in the untreated mice as evidenced by elevated levels of malondialdehyde, ROS levels and hydroperoxides in the striatum (cytosol and mitochondria), while CA prophylaxis completely attenuated the 3-NPA-induced oxidative stress. 3-NPA also caused significant oxidative stress and protein oxidation in cytosol/mitochondria of other brain regions as well which were predominantly abolished by CA prophylaxis. Significant depletion of GSH levels, total thiols and perturbations in antioxidant enzymic defences in striatum and other brain regions discernible among 3-NPA administered mice were also protected with CA prophylaxis. Interestingly, CA prophylaxis offered varying degree of protection against 3-NPA-induced mitochondrial dysfunctions viz., reduction in the activity of succinic dehydrogenase, ETC enzymes and decreased mitochondrial viability. Collectively these findings clearly suggest that short-term oral intake of a standardized aqueous extract of CA confers marked resistance against the 3-NPA-induced oxidative stress and mitochondrial dysfunctions in brain. Although the precise mechanism/s underlying the prophylactic efficacy of CA merit further investigation, based on these findings, it is hypothesized that it may be wholly or in part related to the enhancement of GSH, thiols and antioxidant machinery in the brain regions of prepubertal mice.     

Interrelationships Between BDNF,Superoxide Dismutase,and Cognitive Impairment in Drug-Naive First-Episode Patients With Schizophrenia

The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ.     

Differential expression of superoxide dismutase isoforms in neuronal and glial compartments in the course of excitotoxically mediated neurodegeneration: Relation to oxidative and nitrergic stress

To examine the cellular distribution of radical scavenging enzymes in glia, in comparison to that in neurons and their behaviour during excitotoxically induced neurodegenerative processes, protein levels and the cellular localization of cytosolic and mitochondrial superoxide dismutase (Cu/Zn- and Mn-SOD) were investigated in the rat brain undergoing quinolinic acid (Quin)-induced neurodegeneration. Evidence for the specificity of the applied antibodies to detect immunocytochemically these SOD isoforms was obtained from electron microscopy and Western blotting. In control striatum Mn-SOD was clearly confined to neurons, whereas Cu/Zn-SOD was found, rather delicately, only in astrocytes. Microglia failed to stain with antibodies to both SOD isoforms. Quin application resulted in an initial formation of oxygen and nitrogen radicals as determined by the decline in the ratio of ascorbic to dehydroascorbic acid and by increased levels of nitrated proteins, an indicator for elevated peroxynitrite formation. Morphologically, massive neuronal damage was seen in parallel. Astroglia remained intact but showed initially decreased glutamine synthetase activities. The levels of Mn-SOD protein increased 2-fold 24 h after Quin injection (Western blotting) and declined only slowly over the time period considered (10 days). Cu/Zn-SOD levels increased only 1.3-fold. Immunocytochemical studies revealed that the increase in Mn-SOD is confined to neurons, whereas that of Cu/Zn-SOD was observed only in astroglial cells. Quiescent microglial cells were, as a rule, free of immunocytochemically detectable SOD, whereas in activated microglia a few Mn-SOD immunolabeled mitochondria occurred. Our results suggest a differential protective response in the Quin lesioned striatum in that Mn-SOD is upregulated in neurons and Cu/Zn-SOD in astroglia. Both SOD-isoforms are assumed to be induced to prevent oxidative and nitric oxide/peroxynitrite-mediated damage. In the border zone of the lesion core this strategy may contribute to resist the noxious stimulus. GLIA 23:285–297, 1998. © 1998 Wiley-Liss, Inc.     

Necrostatin-1在小鼠脊髓损伤后继发性损伤中的作用

目的 探讨Necrostatin-1(Nec-1)在小鼠脊髓损伤后继发性损伤中的作用及机制。方法 将168只健康成年雌性LCR小鼠随机分为4组:对照组（48只）、脊髓损伤组（48只）、溶剂组（36只,鞘内注射4 μl二甲基亚砜）和治疗组[36只,鞘内注射4 μl Nec-1（4 mmol/L）]。采用血管夹钳夹小鼠脊髓建立脊髓损伤模型。伤后6、12、24、48 h采用免疫印迹法检测脊髓组织受体相互作用蛋白（RIP）1、3的表达;伤后24 h采用免疫共沉淀法评估RIP1和RIP3的相互作用;伤后24 h检测脊髓组织丙二醛（MDA）和活性氧簇（ROS）水平,电镜观察小鼠脊髓组织神经元线粒体损伤情况。结果 伤后48 h内,小鼠脊髓RIP1表达水平无明显变化;伤后6 h,小鼠脊髓RIP3表达水平明显增高,持续到伤后48 h。伤后24 h,治疗组和溶剂组RIP1和RIP3的表达水平均无明显差异;正常脊髓组织RIP1和RIP3相互作用较弱,脊髓损伤后RIP1和RIP3相互作用加强,而Nec-1显著抑制RIP1和RIP3相互作用。伤后24 h,脊髓神经元线粒体不同程度受损,而治疗组小鼠脊髓神经元线粒体结构保存相对较好。伤后24 h,脊髓组织MDA和ROS含量明显升高,而Nec-1能明显减少小鼠脊髓MDA和ROS含量。结论 小鼠脊髓损伤后,Nec-1通过抑制RIP1和RIP3的相互作用,进而抑制程序性坏死,减轻脊髓继发性损伤。Nec-1能降低ROS产物,减轻氧化应激损伤,保护线粒体功能。     

N-Acetylcysteine delays age-associated memory impairment in mice: role in synaptic mitochondria

Mitochondrial oxidative damage is implicated in brain aging and in age-related neurodegenerative diseases. Since N-acetylcysteine (NAC) has recently been shown to prevent apoptotic death in neuronal cells and protect synaptic mitochondria proteins from oxidative damage in aged mice, we have investigated whether dietary administration of this thiolic antioxidant retards age-related memory loss. At 48 weeks of age, a control female OF-1 mice group was fed standard food pellets and another group received pellets containing 0.3% (w/w) of NAC. After 23 weeks of this diet, the NAC had partially restored the memory deficit associated with aging in mice. Moreover, the lipid peroxide and protein carbonyl contents of the synaptic mitochondria were significantly decreased in the NAC-supplemented animals in comparison with their age-matched controls. The antioxidant properties and probable action on mitochondrial bioenergetic ability in the synaptic terminals may explain, at least partially, the beneficial action of NAC administration.     

Impaired inflammatory response and increased oxidative stress and neurodegeneration after brain injury in interleukin-6-deficient mice

In order to determine the role of the neuropoietic cytokine interleukin-6 (IL-6) during the first 3 weeks after a focal brain injury, we examined the inflammatory response, oxidative stress and neuronal survival in normal and interleukin-6-deficient (knockout, IL-6KO) mice subjected to a cortical freeze lesion. In normal mice, the brain injury was followed by reactive astrogliosis and recruitment of macrophages from 1 day postlesion (dpl), peaking at 3-10 dpl, and by 20 dpl the transient immunoreactions were decreased, and a glial scar was present. In IL-6KO mice, the reactive astrogliosis and recruitment of macrophages were decreased throughout the experimental period. The expression of the antioxidant and anti-apoptotic factors metallothionein I+II (MT-I+II) was increased prominently by the freeze lesion, but this response was significantly reduced in the IL-6 KO mice. By contrast, the expression of the antioxidants Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-SOD, and catalase remained unaffected by the IL-6 deficiency. The lesioned mice showed increased oxidative stress, as judged by malondialdehyde (MDA) and nitrotyrosine (NITT) levels and by formation of inducible nitric oxide synthase (iNOS). IL-6KO mice showed higher levels of MDA, NITT, and iNOS than did normal mice. Concomitantly, in IL-6KO mice the number of apoptotic neurons was significantly increased as judged by TUNEL staining, and regeneration of the tissue was delayed relative to normal mice. The changes in neuronal tissue damage and in brain regeneration observed in IL-6KO mice are likely caused by the IL-6-dependent decrease in MT-I+II expression, indicating IL-6 and MT-I+II as neuroprotective factors during brain injury.     

神经妥乐平通过Nrf2/HO-1/NQO1通路发挥对帕金森病大鼠的神经保护作用

目的 探讨神经妥乐平对帕金森病(PD)大鼠的神经保护作用及其相关机制.方法 SD大鼠分为对照组、PD组(PD造模)、神经妥乐平低剂量组(PD造模+腹腔注射0.6 Nu·kg-1神经妥乐平溶液)、神经妥乐平高剂量组(PD造模+腹腔注射1.2 Nu·kg-1 神经妥乐平溶液)和通路抑制组(PD造模+腹腔注射1.2 Nu·k...