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目的研究SIRT3在褪黑激素保护帕金森病(Parkinson’s disease,PD)多巴胺能神经元中的作用。方法48只小鼠随机分为对照组、模型组和治疗组,治疗组小鼠给予褪黑激素(10 mg·kg-1)和MPTP(30 mg·kg-1)腹腔注射,模型组小鼠给予MPTP腹腔注射,对照组小鼠同时给予等量生理盐水,褪黑激素连续给药14 d。采用免疫组化分析黑质TH、Iba-1表达情况,ELISA法检测中脑组织氧化应激指标(ROS、MDA、SOD)及炎症因子(TNF-α、IL-1β)水平,实时定量PCR分析SIRT3 mRNA水平,免疫荧光和Western blot检测蛋白表达情况。结果与对照组比较,模型组小鼠黑质TH表达减少、Iba-1表达增多,中脑组织氧化应激与炎症损伤明显增强,黑质SIRT3 mRNA和蛋白表达水平明显降低,SOD2蛋白表达减少,iNOS蛋白表达增多,组间比较差异均具有统计学意义( P <0.05)。治疗组小鼠经褪黑激素干预后,TH表达增多、Iba-1表达减少,氧化应激与炎症损伤明显减弱,SIRT3 mRNA和蛋白表达水平升高,SOD2蛋白表达上调,iNOS蛋白表达下调,与模型组比较,差异均具有统计学意义( P <0.05)。 结论 褪黑激素通过上调SIRT3表达抵抗PD多巴胺能神经元损伤,作用机制与其抑制小胶质细胞激活减轻氧化应激和炎症损伤有关。 相似文献
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目的 研究咖啡因对谷氨酸诱导的神经元凋亡是否具有保护作用,并对其机制进行探讨。方法 采用DNA凝胶电泳分析及Hoechst33258核染色方法进行凋亡分析;使用荧光指示试剂Fura 2检测单细胞内游离钙浓度变化。结果 谷氨酸可诱导小脑颗粒神经元凋亡,咖啡因能拮抗谷氨酸的这一效应,其IC50为5-0mmol·L-1。咖啡因的这一保护作用不能被forskolin模拟,也不能被Rp cAMP阻断。此外,内质网Ryanodine受体阻断剂dantrolene也不能取消咖啡因的保护作用,咖啡因不影响谷氨酸诱导的钙超载。结论 咖啡因对谷氨酸诱导的神经元凋亡具有保护作用,这一保护作用与咖啡因升高细胞内cAMP和Ca2+水平的药理作用无关。 相似文献
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目的 研究褪黑激素(Mel)对老年小鼠大脑皮层突触体内钙含量以及激动剂动诱发的新生小鼠脑细胞(Ca^2+)升高的影响,以探讨Mel抗衰老的作用机理。方法 钙离子荧光染料Fura-2AM负载已制备的突触体或细胞,RF-5000型双波长荧光分光光度计测定(Ca^2+)i,结果:长期使用Mel抑制老年小鼠大脑皮层Ca^2+超负荷,Mel也降低钙通道激活剂Bay-K8644,高浓度氯化钾(KCl)和谷氨酸 相似文献
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目的 研究藻酸双酯钠(PSS) 对蜂毒肽(mastoparan)诱导的皮质神经元凋亡是否具有保护作用。方法 体外培养大鼠皮质神经元,定性定量检测细胞凋亡:①用FDA(fluo rescein diacetate) 染色检测细胞存活率,用Hoechst 33258 染色,分析细胞核的形态变化;②琼脂糖凝胶电泳分析DNA 断裂;③流式细胞仪对细胞凋亡峰进行定量分析。结果 PSS使皮质神经元存活率增加,使mastoparan 引起的细胞核固缩、凝聚和断裂现象消失;mastoparan 使神经元的DNA电泳图谱出现明显的“梯子状”,而PSS使此现象消失;mastoparan使神经元的流式细胞仪分析图上出现明显的凋亡峰,PSS可使此凋亡峰消失。结论 藻酸双酯钠对蜂毒肽诱导的皮质神经元凋亡具有明显的保护作用 相似文献
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目的研究木犀草素对于皮层神经元氧化损伤的保护作用及其机制。方法用200μmol·L-1H2O2处理皮层神经元造成神经元的氧化损伤,用LDH活性检测细胞死亡,MTT测定线粒体活性,荧光分光检测神经元线粒体膜电位,细胞内ROS的积累以及过氧化氢酶和谷胱甘肽的含量变化。结果20μmol·L-1的木犀草素能有效的保护H2O2导致的神经元死亡,有效维护线粒体膜电位和线粒体活性,减少细胞内ROS的累积,并能通过提高细胞内谷胱甘肽的含量有效对抗氧化损伤,同时对于H2O2造成的过氧化氢酶活力和谷胱甘肽含量的急剧下降也有很好的保护作用。结论木犀草素是一种比较有效的对抗神经元氧化损伤的保护剂,它很可能通过维持线粒体的活性而达到神经保护作用,并通过提高细胞内谷胱甘肽的水平,增强神经元抗氧化损伤的能力。 相似文献
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褪黑激素是松果体分泌的一类激素,对其研究起初主要集中在调节睡眠的作用,但近年发现其具有强大的抗氧化应激作用。实验研究表明,褪黑激素不仅本身具有明显的抗氧化作用,且被氧化后的多级代谢产物亦有强大的抗氧化功能;还具有同时清除氧族和氮族自由基的双重功效及上调多种抗氧化酶活性的功能。目前对于它在缺血再灌注损伤、抗癌、抗退行性变等领域的应用研究取得众多进展。本文主要综述近年来褪黑激素抗氧化机制及其应用的研究进展。 相似文献
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目的:探究扇贝多肽对大鼠大脑中动脉缺血再灌注模型(MCAO)损伤后神经元的保护作用,并探讨其作用机理。方法:Wistar大鼠 64只随机分为 4组:假手术组、扇贝多肽治疗组、蒸馏水组和模型组。利用焦油紫染色观察大鼠脑缺血区神经元;酶法测定脑组织匀浆抗氧化酶(SOD、GSH-Px)的活性和MDA的含量。结果:焦油紫染色观察发现模型组顶叶缺血神经细胞呈重度缺血样变性,而扇贝多肽组则表现为神经元轻度缺血样变性,说明扇贝多肽能减轻顶叶缺血区神经细胞的损伤程度。模型组脑组织匀浆中 SOD的活性(x±s)为 74.65±17.18 Nu·mL~(-1)、GSH-Px活性为 21.29±3.07U,MDA含量为 79.65±15.62;扇贝多肽组脑组织匀浆中SOD的活性(x±s)为120.37±20.35 Nu·mL~(-1)、GSH-Px活性为29.38±2.15U、MDA含量为 39.56±13.19,与模型组比较,扇贝多肽组脑组织匀浆中 SOD、GSH-Px活性显著提高,MDA含量明显降低(P<0.01)。结论:扇贝多肽对大鼠大脑中动脉缺血再灌注损伤后的神经元具有保护作用。其机制与扇贝多肽能提高抗氧化酶含量,抑制脂质过氧化有关。 相似文献
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近来发现松果腺分泌的褪黑素是一种比维生素E更有效的自由基清除剂和抗氧化剂。褪黑素具有无毒、易穿透生理解剖屏障和进入亚细胞成分的特点。它可通过供电子直接灭活毒性自由基,并明显增强机体抗氧化防御系统。实验证明,褪黑素能拮抗致癌剂黄樟精、百草枯和脂多糖所致的氧化性肝损伤,有效地保护细胞核DNA和脂质膜免受氧化性损伤,刺激谷胱甘肽过氧化物酶和谷胱甘肽还原酶等机体重要的抗氧化酶活性。此外,还发现褪黑素可在促进大鼠切除肝脏再生的同时,影响淋巴细胞亚群分布,调节肝脏药物代谢酶和防止胸腺细胞凋亡。这些研究结果提示,褪黑素的神经免疫调节作用也可能有利于机体抵抗氧化性肝损伤。 相似文献
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目的探讨褪黑素(MEL)对年龄相关性黄斑变性(AMD)模型小鼠视网膜氧化损伤的保护作用及对沉默信息调节因子1/叉头状转录因子1(SIRT1/FOXO1)通路的影响。方法 90只小鼠按随机数字表法分为正常组,模型组,MEL低、中、高剂量组,每组18只。除正常组外,其余各组尾静脉注射25μL/g NaIO3制备AMD小鼠模型,MEL低、中、高剂量组分别以10、20、40 mg/kg MEL灌胃,正常组、模型组灌胃等体积生理盐水,1次/d,连续1周。眼底荧光造影仪进行荧光素眼底血管造影(FFA),光学相干断层扫描(OCT)检测视网膜厚度;HE染色检测视网膜形态;试剂盒检测眼眶静脉血血清中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性;Westernblot法检测小鼠视网膜中SIRT1、FOXO1、Ac-FOXO1蛋白水平。结果模型组视盘消失,血管出现收缩现象,视网膜变白,血管出现破裂,视网膜各层细胞排列紊乱,外核层排列松散,细胞嵌入内节段/外节段,内核层细胞变大且松散排列;随MEL剂量的升高,上述症状均逐渐改善。与正常组相比,模型组视网膜厚度,眼眶静脉... 相似文献
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Introduction: Pesticides are among the most important chemicals used in agriculture sector. However, their extensive use has polluted the environment and increased human vulnerability to various chronic diseases. Pesticide exposure causes genetic and epigenetic modifications, endocrine disruption, mitochondrial dysfunction and oxidative stress. Areas covered: This review is based on the literature studies currently reported on pesticide-induced toxicity and the protective role of melatonin. Scientific databases such as PubMed, Scopus and Web of Science were searched using keywords ‘pesticide’ and ‘melatonin’ up to January 2016. Full length articles related to animal and human exposure were retrieved. A total number of 181 records were obtained, and after excluding the duplicates, 97 papers were further screened on the basis of relevance to the topic. Expert opinion: Melatonin as a broad-spectrum antioxidant is able to penetrate cellular compartments specifically the mitochondria. It is a potent free radical scavenger with low toxicity and desirable solubility in organic and aqueous phases. We are of the opinion that melatonin is a promising agent in minimizing organ injuries induced by pesticides. 相似文献
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目的:探讨mTOR信号介导的自噬在褪黑素(melatonin,Mel)减轻自然衰老SD大鼠肾脏损害的作用及机制.方法:将40只8周龄SD大鼠随机分为4组,空白对照组(A组)、单纯褪黑素处理组(褪黑素10 mg·kg-1·d-1,B组)、老年模型组(C组)和褪黑素干预老年模型组(褪黑素10 mg·kg-1·d-1,D组)... 相似文献
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1. Hyperbaric oxygen (HBO) is a widely used treatment modality in many diseases. A known side-effect of HBO is the production of reactive oxygen species (ROS). Many anti-oxidants, such as vitamins C and E, riboflavin and selenium, have been used successfully to scavenge the ROS produced by HBO administration. 2. The aim of the present study was to determine whether melatonin, a newly discovered anti-oxidant, has a protective effect against the overproduction of ROS produced by HBO in rat brain tissue. 3. Seventy male Sprague-Dawley rats were divided into seven groups as follows: 1, daytime control; 2, daytime HBO; 3, melatonin; 4, daytime HBO plus melatonin; 5, night-time control; 6, night-time HBO; and 7, night-time HBO under light exposure. 4. Hyperbaric oxygen was administered at 303 kPa for 120 min. Melatonin was injected at a dose of 10 mg/kg, i.p. Brain malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were measured to elucidate oxidant status. 4. The MDA and SOD levels of groups 2 and 7 increased significantly. Exogenous (group 4) and endogenous (group 6) melatonin protected against HBO-induced lipid peroxidation. Exogenously administered melatonin (groups 3 and 4) had increased levels of the anti-oxidant enzymes SOD and GPx. 5. In conclusion, HBO caused oxidative stress and melatonin exhibited protective effects. Both endogenously produced and exogenously administered melatonin were found to be effective. 相似文献
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目的:研究褪黑素(melatonin;MT)对谷氨酸(L-glutamate;L-Glu)引起的神经细胞损伤及一氧化氮释放增加的影响.方法:取乳大鼠的神经细胞进行原代培养,加入谷氨酸造成神经元损伤模型;分别以四甲基偶氮唑蓝比色(MTT)法测定细胞存活率,Gress法测定一氧化氮的释放量,通过这两种指标考察MT对谷氨酸神经毒性的对抗作用.结果:谷氨酸500μmol·L-1造成神经细胞的MTT活性显著降低(P<0.05),同时一氧化氮释放量非常显著的增加(P<0.01);而MT(10-5,10-4 mol·L-1)可使MTT活性显著增强(P<0.05,P<0.01),同时亦明显抑制一氧化氮的释放(P<0.05).结论:提示MT可通过抑制谷氨酸引起的一氧化氮释放增加对抗其神经毒性,保护神经细胞免受损伤. 相似文献
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目的 探讨外源性褪黑素(MLT)对在体大鼠心肌急性缺血再灌注损伤的保护作用。方法 36只大鼠随机分为对照组、缺血再灌注(I/R)组及缺血再灌注+褪黑素(I/R+MLT)组,I/R组及I/R+MLT组在体大鼠心脏左冠状动脉前降支完全阻断10min,再灌15min,术中监测记录心电及血流动力学的变化,随后测定局部受损心肌中MDA(丙二醛)的含量和SOD(超氧化物歧化酶)的活性并用电镜检查心肌结构。结果心脏血流动力学指标I/R+MLT组好于I/R组(P<0 .01);I/R组MDA的含量明显高于对照组及I/R+MLT组(P<0.01 ),SOD活性明显低于对照组及I/R+MLT组(P<0 .01),I/R+MLT组MDA含量及SOD活性与对照组无明显差异(P>0 .05);电镜下I/R组心肌细胞结构损伤明显,而I/RMLT组心肌细胞结构基本正常。结论 褪黑素对在体大鼠心肌急性缺血再灌注损伤具有保护作用,其作用与抗氧化损伤有关。 相似文献
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目的研究松果体素对培养的大鼠海马神经元甘氨酸激活的全细胞电流(Igly)的调控。方法在培养的大鼠海马神经元上,采用全细胞膜片钳技术,研究松果体素对甘氨酸激活的全细胞电流的调控。结果松果体素以浓度依赖的方式可逆地抑制Igly,并且这种抑制作用是非竞争性的,松果体素的抑制作用没有特异的亚基选择性。结论松果体素能以非竞争的方式直接抑制甘氨酸受体介导的电流,这种抑制作用可能对海马区域神经网络的兴奋性产生影响。 相似文献
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ABSTRACTIntroduction: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease associated with disruption of alveolar epithelial cell layer and expansion of fibroblasts/myofibroblasts. Excessive levels of oxidative/nitrosative stress, induction of apoptosis, and insufficient autophagy may be involved in IPF pathogenesis; hence, the targeting of these pathways may ameliorate IPF. Areas covered: We describe the ameliorative effect of melatonin on IPF. We summarize the research on IPF pathogenesis with a focus on oxidative/nitrosative stress, autophagy and apoptosis pathways and discuss the potential effects of melatonin on these pathways. Expert opinion: Oxidative/nitrosative stress, apoptosis and autophagy could be interesting targets for therapeutic intervention in IPF. Melatonin, as a potent antioxidant, induces the expression of antioxidant enzymes, scavenges free radicals and modulates apoptosis and autophagy pathways. The effect of melatonin in the induction of autophagy could be an important mechanism against fibrotic process in IPF lungs. Further clinical studies are necessary to determine if melatonin could be a candidate for treating IPF. 相似文献
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Introduction: Cyclophosphamide (CP) is an alkylating antineoplastic agent with known toxicity to the male reproductive system. Areas covered: This review summarizes the known mechanisms by which CP exerts its toxic effects on the male reproductive system and the methods utilized to prevent such effects so that it could be further investigated and applied in clinical use. Keywords including [‘Cyclophosphamide’ AND ’male reproductive’ OR’ sperm toxicity’ OR ’spermatotoxicity’ OR ’infertility] were searched through Google Scholar, PubMed and Scopus databases based on PRISMA guidelines. After removing duplicates and irrelevant data, 76 papers were reviewed concerning the outcomes of treatment of male mice, rats, and humans with CP and the effects of co-administration of various natural and synthetic compounds on male reproductive system. Expert opinion: CP exerts its effect mainly by inducing oxidative stress and changing gene expression in spermatocytes variably during different stages of development. These effects could be either restored or prevented by the administration of compounds with antioxidant properties and those which target the biochemical alterations induced by CP. 相似文献
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