烟酰胺腺嘌呤二核苷酸对小鼠脑血管内皮细胞缺血性损伤的保护作用

目的观察(NAD)对缺糖缺氧引起的脑血管内皮损伤是否具有保护作用。方法采用缺糖缺氧(OGD)作为体外缺血性损伤模型,以(NAMPT)特异性抑制剂降低细胞内的NAD水平,以NAD的前体物质烟酰胺单核苷酸(NMN)增加细胞内NAD水平,观察NAD降低和增加对OGD引起的小鼠来源脑血管内皮细胞(bEnd.3细胞)损伤的影响。结果 FK866时间和浓度依赖的降低细胞内NAD水平及细胞活性,NMN不能增加正常细胞的活性和NAD水平,但可逆转FK866的作用;OGD 70分钟一过性引起细胞活性下降,24 h后细胞活性恢复并伴NAD水平显著下降,降低NAD水平可以增加OGD引起的细胞活性下降,但对恢复无明显影响,NMN对OGD引起的细胞活性及NAD改变均无影响,但可逆转FK866引起的作用;OGD 4 h造成明显的细胞损伤,细胞活性恢复缓慢,但NAD水平不变,降低NAD水平可以增加OGD 4 h引起的细胞损伤并减慢恢复,NMN能增加NAD水平并减轻细胞损伤并促进恢复。结论 NAD对缺糖缺氧引起的小鼠脑血管内皮细胞缺血性损伤具有保护作用,提示NAD可能成为脑缺血的一个保护分子。     

丹红注射液治疗缺血性脑病34例临床总结

脑血管疾病的发病率、病死率和致残率很高,是导致人类死亡的三大疾病之一,病后存活者中残障率达75%,给患者及其家庭、社会带来沉重负担。缺血性脑病是其中之一,因此缺血性脑病的防治成为社会和医学界关注的重要课题。现代医学研究认为,脑缺血再灌注损伤和脑部血流改变是大多数缺血性脑血管疾病的主要病理生理过程,其发生机制主要有自由基学说、钙超载学说、兴奋性氨基酸学说、细胞凋亡学说等。     

缺血性卒中神经元损害的分子瀑及新治疗制剂目标

脑卒中在全世界都是一个主要的死亡和致残原因 ,在所有卒中中 ,缺血性卒中约占 85 % [1 ] ,本文就缺血性卒中引起神经元损害的分子瀑 ( Cascade)及新的治疗制剂目标作一介绍。1　神经元损害的分子瀑见附图。附图　引起神经元损害的分子瀑　　 * VGCC电压控制钙通道A　谷氨酸释放抑制剂 ,B　钙拮抗剂 ,C　 NMDA和 AMPA受体拮抗剂 ,Mg,D　 NOS抑制剂 ,E　抗氧化剂 ,F　粘附分子抗体1 .1　兴奋性氨基酸 ( EAA) :缺血脑组织中有大量 EAA释放。 EAA主要是谷氨酸 ( Glu)和天门冬氨酸 ( ASP) ,Glu正常细胞内高于细胞间隙 1 0 0 0倍 …     

抗氧化剂与胃肠黏膜屏障损伤

<正>1 氧自由基及损伤作用含有一个不成对电子的分子或原子团称自由基。部分氧分子为活性氧簇(reactive oxygen spe- cies,ROS),包括过氧化氢、超氧阴离子自由基、羟自由基、一氧化氮黄嘌呤氧化酶(XO)自由基等。体内自由基的产生和清除应是平衡的,人体才能保持健康。如果自由基产生过多或清除自由基的能力下降,体内就会有多余的自由基(特别是氧自由基),会损伤细胞成分,导致疾病和衰老的发生。 ROS是许多疾病的特征。自由基和多种疾病有关, 包括与胃肠黏膜屏障损伤密切相关。各器官均有防御ROS形成即清除氧自由基的机制,从而可快速修复氧自由基造成的损伤。体内自由基清除体系主要包括抗氧化酶和抗氧化剂两类。自由基也涉及信号传导通路,如XO既参与传导,同时也是自由基清除剂。     

72例急性脑血管病人血浆过氧化脂质和红细胞超氧化物歧化酶含量观察

近年来,随着自由基生物学和自由基医学的飞跃发展,人们对自由基冲击下的脂质过氧化损伤,造成生物结构和功能障碍,导致衰老和引起多种疾病予以极大的关注。过氧化脂质(LPO)可使浆膜和亚微结构细胞器如线粒体、内质网和溶酶体等生物膜内多不饱和脂肪酸过氧化,导致一系列细胞功能和结构的变化。在缺血性脑损伤中,脂质过氧化反应是造成不可逆性脑损伤的重要因素。脑出血后继发性脑损伤的病理机制     

抗再灌注损伤减轻家兔肝脏常温缺血损害的实验研究

抗再灌注损伤减轻家兔肝脏常温缺血损害的实验研究福建医学院附属第一医院李旭近年来，器官缺血性损害研究的一个重要方面是再灌注损伤。氧自由基的脂质过氧化作用以及细胞内钙离子超负荷是引起再灌注损伤的两个重要机制。根据这些损伤机理，本实验通过抗氧化剂和钙离子拮...     

抗氧化剂治疗小儿病毒性心肌炎32例疗效观察

近年来对活性氧引起的细胞损伤导致一些疾病,引起了广泛重视,一些学者认为,在病毒性心肌炎的发病机理中,为活性氧增加产生超氧阴离子自由基,引发脂质过氧化作用导致心肌损害有关,维生素C、维生素E辅酶Q10等为有效的自由基清除剂,被用于病毒性心肌炎的治疗。为观察抗氧化剂治疗病毒性心肌炎的疗效,我科对1999－01－2000－10收治的32例病毒性心肌炎患儿随机分为治疗组、对照组,对抗氧化剂疗效进行了对比观察,现将观察结果报告如下。     

脑缺血再灌注神经细胞凋亡机制研究进展

脑缺血是由于血栓或栓子阻塞脑内动脉而导致血管闭塞,引起脑组织缺血缺氧、神经元受损的一系列临床症状和体征。目前缺血性脑血管疾病治疗的最佳方案是脑梗死后超早期溶栓,尽早恢复缺血区域血流再灌注,挽救缺血脑组织。但在缺血性疾病抢救和治疗过程中,医学家们渐渐发现,对组织造成损伤的主要因素,不是缺血本身,而是恢复血液供应后导致严重的迟发性神经元损伤,即引起脑缺血再灌注损伤。许多研究表明脑缺血再灌注损伤与神经细胞凋亡有着密切的关系,大多数学者认为,细胞凋亡的发生不仅是凋亡相关基因表达的结果,而且受许多内外因素的调节。目前,研究证据表明,脑缺血再灌注后神经元凋亡可能与以下几个因素有关:(1)缺血缺氧本身激活凋亡发生基因,例如促凋亡基因Bax、缺氧诱导因子1α(HIF-1α)、T淋巴细胞、趋化因子等的激活;(2) mi RNA、蛋白激酶ERK等凋亡蛋白因子及有关的细胞因子产生;(3)脑缺血再灌注后产生大量氧自由基(ROS)、氮自由基(RNS)以及NADPH化酶(NOX)对神经元造成严重损伤的同时,也诱导凋亡的发生;(4)钙超载激活一系列钙依赖性酶促反应,促进凋亡的发生;(5)线粒体损伤导致细胞能量代谢障碍。本文将从以上几个方面详细阐述神经元凋亡发生机制以及作用于脑缺血再灌注损伤不同通路、不同因子的药物。     

胆红素水平与缺血性脑卒中的临床相关性

脑血管病目前已经上升到我国致死致残疾病中的第一位。其中70%的患者为缺血性脑卒中(IS),其主要病理因素是血管动脉粥样硬化。缺血性脑血管病(ischemic cerebrovascular disease,ICVD)为目前危害生命健康的一种最常见的病症,缺血性脑卒中的发病率、病死率、致残率均相对较高,而中老年为高发人群。其主要包括以下几种,短暂性脑缺血发作(transient ischemic attack,TIA)、腔隙性脑梗死、脑血栓形成、脑栓塞以及分水岭梗死。还有一种缺血性脑血管病为"椎-基底动脉供血不足"。脑血管类疾病是患者的血管壁病变或者患者的本身血流动力学障碍的一些相关基础上发生的血液供应上的障碍,现对应的相应的供血区的缺氧以及缺血,并引起损害,造成一系列继发的一些临床症状及一些功能的缺损。此类疾病的发病过程主要涉及到动脉硬化,动脉硬化是为常见的病因,其中血脂异常又是动脉硬化的最重要危险因素;而氧化应激又是动脉硬化的过程中其细胞损伤的一个主要机制,自由基是介导该效应的主要因素。胆红素的意义为,血清胆红素被认为是毒性代谢产物,在临床实践中胆红素一直被作为其肝脏以及造血系统等一些疾病的一个标志物。以松原市中心医院一年内脑血管病患者仔细筛查后,符合研究条件的患者在进行记录与检测血清胆红素与缺血性脑卒中之间的关系的一些相关数据。根据不同病情,不同采血时间,不同发病状态,不同神经症状,不同身体一般指标,来分组对照,研究,并且详细记录分析。研究关于胆红素水平升高在脑血管疾病中的机制作用,研究胆红素水平升高,动脉硬化,短暂性脑缺血发作,椎-基底动脉供血不足,脑梗死之间的关系。胆红素在缺血性脑血管疾病预测及治疗方面的展望:胆红素水平在缺血性脑卒中的治疗与预防诊断中,给予临床治疗中重要的意义。     

低分子右旋糖酐-40致急性肾损伤15例分析

<正>右旋糖酐-40为许多脱水葡萄糖分子的聚合物,能扩充血容量、降低血黏度、改善微循环,在内科被广泛用于缺血性脑血管疾病及蛛网膜下腔出血继发脑血管痉挛的治疗。但右旋糖酐-40在体内以肾脏排泄为主,有引起或促进急性肾损伤(AKI)的不良反应。我科于2004年1月至     

Antioxidant therapy in acute central nervous system injury: current state

Free radicals are highly reactive molecules generated predominantly during cellular respiration and normal metabolism. Imbalance between cellular production of free radicals and the ability of cells to defend against them is referred to as oxidative stress (OS). OS has been implicated as a potential contributor to the pathogenesis of acute central nervous system (CNS) injury. After brain injury by ischemic or hemorrhagic stroke or trauma, the production of reactive oxygen species (ROS) may increase, sometimes drastically, leading to tissue damage via several different cellular molecular pathways. Radicals can cause damage to cardinal cellular components such as lipids, proteins, and nucleic acids (e.g., DNA), leading to subsequent cell death by modes of necrosis or apoptosis. The damage can become more widespread due to weakened cellular antioxidant defense systems. Moreover, acute brain injury increases the levels of excitotoxic amino acids (such as glutamate), which also produce ROS, thereby promoting parenchymatous destruction. Therefore, treatment with antioxidants may theoretically act to prevent propagation of tissue damage and improve both the survival and neurological outcome. Several such agents of widely varying chemical structures have been investigated as therapeutic agents for acute CNS injury. Although a few of the antioxidants showed some efficacy in animal models or in small clinical studies, these findings have not been supported in comprehensive, controlled trials in patients. Reasons for these equivocal results may include, in part, inappropriate timing of administration or suboptimal drug levels at the target site in CNS. Better understanding of the pathological mechanisms of acute CNS injury would characterize the exact primary targets for drug intervention. Improved antioxidant design should take into consideration the relevant and specific harmful free radical, blood brain barrier (BBB) permeability, dose, and time administration. Novel combinations of drugs providing protection against various types injuries will probably exploit the potential synergistic effects of antioxidants in stroke.     

Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options

Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimer’s disease, Parkinson’s disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario.Key Words: ROS, oxidative stress, antioxidants, neurodegenerative diseases, rns, amyloid, catalase, phagocytes.     

Novel Therapeutic Targets in Depression and Anxiety: Antioxidants as a Candidate Treatment

There is growing evidence that the imbalance between oxidative stress and the antioxidant defense system may be associated with the development neuropsychiatric disorders, such as depression and anxiety. Major depression and anxiety are presently correlated with a lowered total antioxidant state and by an activated oxidative stress (OS) pathway. The classical antidepressants may produce therapeutic effects other than regulation of monoamines by increasing the antioxidant levels and normalizing the damage caused by OS processes. This chapter provides an overview of recent work on oxidative stress markers in the animal models of depression and anxiety, as well as patients with the aforementioned mood disorders. It is well documented that antioxidants can remove the reactive oxygen species (ROS) and reactive nitrogen species (RNS) through scavenging radicals and suppressing the OS pathway, which further protect against neuronal damage caused oxidative or nitrosative stress sources in the brain, hopefully resulting in remission of depression or anxiety symptoms. The functional understanding of the relationship between oxidative stress and depression and anxiety may pave the way for discovery of novel targets for treatment of neuropsychiatric disorders.     

Evaluation of Antioxidant Producing Potential of Halophilic Bacterial Bionts from Marine Invertebrates

Marine invertebrates exposed to high levels of reactive oxygen species in the oceans have been reported to produce antioxidants as a major defense against free radical mediated toxicity; protecting their tissues from the damage associated with the oxidative stress. In view of this, the present study was carried out to determine the antioxidant activity of 100 bacterial bionts isolated from marine sponges, corals and a single bivalve. Methanol extract of biont GUVFCFM-3 produced 67.83% scavenging of 2,2-diphenyl-2-picrylhydrazyl free radicals and 65.87% scavenging of superoxide free radicals. Preliminary tests leading to the identification of the extracellular antioxidant factor produced by GUVFCFM-3 revealed that it is a peptide. We report that the genera Chromohalobacter sp. primarily known for its unique salt tolerating abilities by virtue of the production of osmolytes is an excellent scavenger of free radicals.     

Galangin (3,5,7-Trihydroxyflavone) Shields Human Keratinocytes from Ultraviolet B-Induced Oxidative Stress

Most skin damage caused by ultraviolet B (UVB) radiation is owing to the generation of reactive oxygen species. Phytochemicals can act as antioxidants against UVB-induced oxidative stress. This study investigated the protective effects of the flavone galangin against UVB-induced oxidative damage in human keratinocytes. Galangin efficiently scavenged free radicals and reduced UVB-induced damage to cellular macromolecules, such as DNA, lipids, and proteins. Furthermore, galangin rescued cells undergoing apoptosis induced by UVB radiation via recovering mitochondrial polarization and down-regulating apoptotic proteins. These results showed that galangin protects human keratinocytes against UVB radiation-induced cellular damage and apoptosis via its antioxidant effects.     

Oxidative stress induced mitochondrial DNA deletion as a hallmark for the drug development in the context of the cerebrovascular diseases

Oxidative stress in the cardiovascular system, including brain microvessels and/or parenchymal cells results in an accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) compounds thus promoting leukocyte adhesion and increasing endothelial permeability. The resulting chronic injury stimulus results in progressive cellular hypometabolism. We propose that hypometabolism, coupled with oxidative stressors, is responsible for most Alzheimer disease (AD) and cerebrovascular accidents (CVAs) and appears to be a central initiating factor for vascular abnormalities, mitochondrial damage and an imbalance in the activity of vasoactive substances, such as different isoforms of nitric oxide synthase (NOS), endothelin-1 (ET-1), oxidative stress markers, mtDNA and mitochondrial enzymes in the vascular wall and in brain parenchymal cells. At higher concentrations, ROS induces cell injury and death, which occurs during the aging process, where accelerated generation of ROS and a gradual decline in cellular antioxidant defense mechanisms, especially in the mitochondria. Vascular endothelial and neuronal mitochondria are especially vulnerable to oxidative stress due to their role in energy supply and use, which can cause a cascade of debilitating factors such as the production of giant and/or vulnerable young mitochondrion who's DNA has been compromised. Therefore, mitochondrial DNA abnormalities such as overproliferation and or deletion can be used as a key marker for diseases differentiation and effectiveness of the treatment. We speculate that specific antioxidants such as acetyl-L-carnitine and R-alpha lipoic acid seem to be potential treatments for AD. They target the factors that damage mitochondria and reverse its effect, thus eliminating the imbalance seen in energy production and restore the normal cellular function, making these antioxidants very powerful alternate strategies for the treatment of cardiovascular cerebrovascular as well as neurodegenerative diseases including AD. Future potential exploration using mtDNA markers can be considered more accurate hallmarks for diagnosis and monitoring treatment of human diseases. The present article discusses some of the patents regarding the oxidative stress.     

Relative impact of oxidative stress on male reproductive function

Impairment of normal spermatogenesis and sperm function are the most common causes of male factor infertility. Abnormal sperm function is difficult to evaluate and treat. There is a lack of understanding of the factors contributing to normal and abnormal sperm function leading to infertility. Many recent studies indicate that oxygen-derived free radicals induce damage to spermatozoa. The excessive generation of these reactive oxygen species (superoxide, hydroxyl, nitric oxide, peroxide, peroxynitrile) by immature and abnormal spermatozoa and by contaminating leukocytes associated with genitourinary tract inflammation have been identified with idiopathic male infertility. Mammalian spermatozoa membranes are rich in polyunsaturated fatty acids. This makes them very susceptible to oxygen-induced damage, which is mediated by lipid peroxidation. In a normal situation, the antioxidant mechanisms present in the reproductive tissues and their secretions are likely to quench these reactive oxygen species (ROS) and protect against oxidative damage to gonadal cells and mature spermatozoa. During chronic disease states, aging, toxin exposure, or genitourinary infection/inflammation, these cellular antioxidant mechanisms downplay and create a situation called oxidative stress. Thus, a balance between ROS generation and antioxidant capacity plays a critical role in the pathophysiology of disease state. Recent efforts towards the development of new reliable assays to evaluate this oxidative stress status have resulted in the establishment of ROS-TAC score. Such assessment of oxidative stress status (OSS) may help in designing newer modes of male factor infertility treatment by suitable antioxidants.     

Role of oxidative stress and antioxidant therapy in acute and chronic phases of sulfur mustard injuries: a review

Sulfur mustard (SM) is a chemical compound that preferentially targets ocular, cutaneous and pulmonary tissues. Although pathologic effect of SM has been extensively considered, molecular and cellular mechanism of its toxicity, especially at the chronic phase of injury is not well-understood. Excessive production of reactive oxygen species (ROS) and oxidative stress (OS) appears to be involved in SM-induced injuries. SM may trigger several molecular and cellular pathways linked to OS and inflammation that can subsequently result in cell death and apoptosis. At the acute phase of injury, SM can enhance ROS production and OS by reducing the activity of antioxidants, depletion of intercellular glutathione (GSH), decreasing the productivity of GSH-dependent antioxidants, mitochondrial deficiency, accumulation of leukocytes and pro-inflammatory cytokines. Overexpression of ROS producing enzymes and down-regulation of antioxidant enzymes are probably the major events by which SM leads to OS at the chronic phase of injury. Therefore, antioxidant therapy with potent antioxidants such as N-acetylcysteine and curcumin may be helpful to mitigate SM-induced OS damages. This review aims to discuss the proposed cellular and molecular mechanisms of acute and delayed SM toxicity, the importance of OS and mechanisms by which SM increases OS either at the acute or chronic phases of injuries along with research on antioxidant therapy as a suitable antidote.     

Diabetes mellitus and oxidative stress—A concise review

Human body is continuously exposed to different types of agents that results in the production of reactive species called as free radicals (ROS/RNS) which by the transfer of their free unpaired electron causes the oxidation of cellular machinery. In order to encounter the deleterious effects of such species, body has got endogenous antioxidant systems or it obtains exogenous antioxidants from diet that neutralizes such species and keeps the homeostasis of body. Any imbalance between the RS and antioxidants leads to produce a condition known as “oxidative stress” that results in the development of pathological condition among which one is diabetes. Most of the studies reveal the inference of oxidative stress in diabetes pathogenesis by the alteration in enzymatic systems, lipid peroxidation, impaired Glutathione metabolism and decreased Vitamin C levels. Lipids, proteins, DNA damage, Glutathione, catalane and superoxide dismutase are various biomarkers of oxidative stress in diabetes mellitus. Oxidative stress induced complications of diabetes may include stroke, neuropathy, retinopathy and nephropathy. The basic aim of this review was to summarize the basics of oxidative stress in diabetes mellitus.     

Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection

Our review aims to examine the cellular and molecular mechanisms of cardiovascular protection of green tea polyphenols, particularly epigallocatechin gallate (EGCG), which focuses on the anti-oxidative and anti-inflammatory effects. EGCG is the major and the most active component in green tea. Studies have shown that EGCG protects cellular damage by inhibiting DNA damage and oxidation of LDL. One of the protective properties of EGCG is its ability to scavenge free radicals. EGCG can also reduce the inflammatory response associated with local tissue injuries such as the hepatocellular necrosis in acute liver injury induced by carbon tetrachloride. The protective effect of EGCG is due to its ability to decrease lipid peroxidation, oxidative stress and the production of nitric oxide (NO) radicals by inhibiting the expression of iNOS. EGCG also ameliorates the overproduction of pro-inflammatory cytokines and mediators, reduces the activity of NF-kappaB and AP-1 and the subsequent formation of peroxynitrite with NO and reactive oxygen species. Thus, EGCG effectively mitigates cellular damage by lowering the inflammatory reaction and reducing the lipid peroxidation and NO generated radicals leading to the oxidative stress. Green tea is proposed to be a dietary supplement in the prevention of cardiovascular diseases in which oxidative stress and proinflammation are the principal causes.