抗氧化剂改善卵母细胞线粒体功能和不孕女性生育结局的研究进展

线粒体是体内产生能量的工厂,在产生三磷酸腺苷(adenosine triphosphate,ATP)的同时还会产生大量的活性氧(reactive oxygen species,ROS).过多的ROS可诱导氧化应激并最终导致线粒体功能障碍.卵母细胞线粒体功能障碍可导致卵母细胞质量下降,影响胚胎发育和妊娠结局.最新的动物实...     

活性氧与女性生殖

活性氧(reactive oxygen species,ROS)是正常有氧代谢的产物,正常情况下,ROS的产生和清除保持动态平衡,但是当线粒体功能下降,ROS产生增加或细胞抗氧化机制受损时,可造成ROS的累积,导致细胞氧化应激损伤.在腹膜液、卵泡液和输卵管积水等重要的生殖微环境内都检测到ROS的存在,并发现腹腔液内ROS水平与不明原因不孕相关,多种生殖组织内存在不同的氧化/抗氧化系统,ROS可能参与卵母细胞老化、胚胎体外发育不良以及一些不孕原因的形成,在女性生殖中起重要作用.     

氧化应激对男性（雄性）生殖系统的影响

氧化应激可产生活性氧簇（ROS）。正常状况下，低水平ROS具有调节细胞生理功能的作用，而异常高水平的ROS对组织和细胞产生相应的危害，如信号通路异常、能量代谢失调、基因突变和蛋白质结构改变等，进而影响细胞、组织、器官乃至系统的功能。男性（雄性）生殖系统中，高水平的ROS对生殖器官和生殖细胞同样产生严重的危害，如对睾丸的危害可影响其形态学结构及类固醇激素的合成；对生殖细胞可直接损伤精子的DNA、膜脂质和蛋白的结构，使精子的畸形率大幅度上升，最终导致男性（雄性）不育。综述男性（雄性）生殖系统ROS的产生及其对生殖的影响，对了解临床男性不育症的发病机制及治疗具有重要的意义。     

氧化应激对卵母细胞发育及体外受精-胚胎移植结局的影响

卵母细胞及胚胎发育的微环境中,由氧气参与新陈代谢所产生的一些活性氧物质如得不到及时清除,会诱导氧化应激的现象.有研究显示,氧化应激是影响卵母细胞质量和胚胎发育潜能的主要因素之一,大量的氧化应激可导致卵母细胞内线粒体形态和功能的改变,进而影响三磷酸腺苷(ATP)合成,干扰卵母细胞内减数分裂,使卵母细胞内非整倍体染色体数目增多,造成胚胎DNA损伤和早期发育停滞,最终导致不良妊娠结局.在体外培养时,经常通过添加外源性抗氧化剂或自由基清除剂,以及建立并维持卵母细胞及胚胎发育所需的低氧环境来拮抗氧化应激的不良作用.就氧化应激的产生、对卵母细胞和胚胎发育的影响及其机制,以及如何拮抗氧化应激的不良影响进行综述.     

活性氧与女性生殖

活性氧(reactive oxygen species,ROS)是正常有氧代谢的产物,正常情况下,ROS的产生和清除保持动态平衡,但是当线粒体功能下降,ROS产生增加或细胞抗氧化机制受损时,可造成ROS的累积,导致细胞氧化应激损伤。在腹膜液、卵泡液和输卵管积水等重要的生殖微环境内都检测到ROS的存在,并发现腹腔液内ROS水平与不明原因不孕相关,多种生殖组织内存在不同的氧化/抗氧化系统,ROS可能参与卵母细胞老化、胚胎体外发育不良以及一些不孕原因的形成,在女性生殖中起重要作用。     

自由基,趋化因子与HIV-1/SIV感染及酒精肝疾病

自由基医学是近30年来迅速发展起来的一门新兴的边缘学科,它为许多疾病的发病原因、发病机制提供了新的理论、新的内涵.生物体内的自由基95%以上是氧自由基,一旦氧自由基产生过多或抗氧化体系出现障碍,体内氧自由基代谢就会出现失衡,产生大量的活性氧(reactive oxygen species,ROS),使机体处于氧化应激状态.氧化应激可导致细胞损伤,引起多种严重疾病.越来越多证据表明,HIV(human immun-odeficiency virus)感染者处于慢性氧化应激状态.笔者对自由基和趋化因子在HIV-1/SIV(Simian immmunodeficiency virus)和酒精肝中对细胞的损伤作用进行了综述.     

氧化应激在卵巢相关生殖障碍疾病中的作用

活性氧（reactive oxygen species,ROS）在生理状态下作为第二信使发挥细胞信号转导作用,当机体受到缺氧、炎症反应等刺激时,体内ROS水平增加,诱导体内发生氧化应激（oxidative stress）反应。适量的ROS促进卵母细胞的第一次减数分裂,并诱导非优势卵泡进入细胞凋亡。研究表明,氧化应激与多囊卵巢综合征（polycystic ovary syndrome,PCOS）患者的高雄激素血症、胰岛素抵抗、排卵障碍和线粒体损伤等有密切联系;应用抗氧化剂控制氧化应激可能成为早发性卵巢功能不全（premature ovarian insufficiency,POI）的辅助治疗方式。氧化应激抑制DNA甲基化酶引起DNA低甲基化、引起微小RNA及相关活性因子的表达异常,参与卵巢肿瘤细胞增殖和耐药性发生。综述氧化应激在PCOS、POI和卵巢肿瘤等卵巢相关生殖障碍疾病中的作用,展望抗氧化应激治疗的可能应用前景。     

不同程度心理应激对小鼠卵巢内氧化应激水平的影响

目的:探讨不同程度刺激对小鼠卵巢氧化应激水平的影响,以期为不孕症患者辅助心理治疗提供理论依据。方法:80只雌鼠随机分为4组,给予不同程度且不可预知性刺激4周,观察小鼠体质量及行为学改变。造模成功后,检测小鼠血清中超氧化物歧化酶(SOD)含量、活性氧(ROS)水平,小鼠卵巢组织中SOD活性、丙二醛(MDA)含量、SOD2、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)3种抗氧化物酶的m RNA水平。结果:不同程度心理应激组与正常组相比,小鼠体质量降低,不动时间和中央区域滞留时间延长,进入中央区域次数及中央区域活动时间减少,差异有统计学意义(P<0.05);血清中ROS水平升高,SOD含量降低,卵巢组织中SOD活性降低,MDA含量升高,SOD2、CAT及GSH-Px活性降低,差异有统计学意义(P<0.05)。结论:心理应激能够降低小鼠的自主活动欲望和探索欲望,ROS的累积引发机体内氧化应激反应,影响女性生殖功能。     

活性氧与女性生殖

活性氧(reactive oxygen species，ROS)是正常有氧代谢的产物，正常情况下，ROS的产生和清除保持动态平衡，但是当线粒体功能下降，ROS产生增加或细胞抗氧化机制受损时，可造成ROS的累积，导致细胞氧化应激损伤。在腹膜液、卵泡液和输卵管积水等重要的生殖微环境内都检测到ROS的存在，并发现腹腔液内ROS水平与不明原因不孕相关，多种生殖组织内存在不同的氧化／抗氧化系统，ROS可能参与卵母细胞老化、胚胎体外发育不良以及一些不孕原因的形成，在女性生殖中起重要作用。     

短期胰岛素泵强化治疗对初诊2型糖尿病患者循环内皮祖细胞水平的影响及其抗氧化机制

目的 观察短期胰岛素泵(CSⅡ)强化治疗对初诊2型糖尿病(T2DM)患者外周血循环内皮祖细胞(EPCs)的保护作用及其抗氧化机制.方法 选取初诊T2DM患者40例(T2DM组),健康体检者30例(对照组),采用密度梯度离心法收集外周血单个核细胞,诱导分化培养7 d后,激光共聚焦显微镜鉴定FITC-UEA和DIL-acLDL双染色阳性细胞为正在分化的EPCs,并在倒置显微镜下计数.采用半自动生化仪测定血清活性氧活力(ROS)、丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD).结果 与对照组比较,T2DM组外周血EPCs减少[(46±3)个比(23±4)个](P<0.01),ROS、MDA增高[分别为(1125±687)U/ml比(2088±765)U/ml、(4.58±3.03)μmol/L比(8.32±4.15)μmol/L](P<0.01),GSH、SOD减低[分别为(263 ±35)mg/L比(206±41)mg/L、(103±7)U/ml比(80±15)U/ml](P<0.05).EPCs与ROS、MDA呈负相关(r=-0.7352,P<0.01;r=-0.8454,P<0.01),与GSH、SOD呈正相关(r=0.5435,P<0.05;r=0.6437,P<0.05).经短期CSⅡ强化治疗后T2DM患者EPCs明显增加(P<0.05),ROS、MDA明显降低(P<0.05),GSH、SOD明显增加(P<0.05).结论 短期CSⅡ强化治疗可明显减轻T2DM患者体内氧化应激,促进EPCs数量的恢复,进而防止血管病变.     

Oxidative stress

Oxidative stress is defined by an imbalance between increased levels of reactive oxygen species (ROS) and a low activity of antioxidant mechanisms. An increased oxidative stress can induce damage to the cellular structure and potentially destroy tissues. However, ROS are needed for adequate cell function, including the production of energy by the mitochondria. Increased oxidative stress has been incriminated in physiological conditions, such as aging and exercise, and in several pathological conditions, including cancer, neurodegenerative diseases, cardiovascular diseases, diabetes, inflammatory diseases, and intoxications. However, prevention by antioxidants has been mostly inefficient. Therefore, a rigorous scientific evaluation in well-defined conditions is mandatory to define the appropriate place for manipulations of the oxidative pathways in human medicine.     

OSAHS与氧化应激及其相关并发症的最新研究进展

阻塞性睡眠呼吸暂停/低通气综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)是最常见的睡眠呼吸障碍性疾病。大量临床研究、细胞培养和动物模型利用间歇性缺氧表明,OSAHS可以导致氧化应激(oxidative stress,OS),并且氧化应激在OSAHS及其合并症的发生和发展中起核心作用。OSAHS的重要致病机制是其特征性的慢性间歇性缺氧,后者可以促进活性氧(reactive oxygen species,ROS)和诱导氧化应激的形成。过量的ROS可以在生理或者病生条件下破坏生物分子、改变细胞功能,如引起胰岛B细胞凋亡及胰岛功能损伤,促进炎症、血管内皮功能障碍和心血管疾病发病率。氧化应激(OS)是OSAHS的重要特征,并能直接促使OSAHS相关并发症如血管内皮异常,高血压,高血脂和2型糖尿病/胰岛素抵抗等疾病的发生与发展。因此,氧化应激是OSAHS及其并发症的发生发展的最重要的环节。现就OS与OSAHS及其并发症的相关性在近几年的最新研究进展作一综述。     

Cardiac Oxidative Stress and the Therapeutic Approaches to the Intake of Antioxidant Supplements and Physical Activity

Reactive oxygen species (ROS) are strongly reactive chemical entities that include oxygen regulated by enzymatic and non-enzymatic antioxidant defense mechanisms. ROS contribute significantly to cell homeostasis in the heart by regulating cell proliferation, differentiation, and excitation-contraction coupling. When ROS generation surpasses the ability of the antioxidant defense mechanisms to buffer them, oxidative stress develops, resulting in cellular and molecular disorders and eventually in heart failure. Oxidative stress is a critical factor in developing hypoxia- and ischemia-reperfusion-related cardiovascular disorders. This article aimed to discuss the role of oxidative stress in the pathophysiology of cardiac diseases such as hypertension and endothelial dysfunction. This review focuses on the various clinical events and oxidative stress associated with cardiovascular pathophysiology, highlighting the benefits of new experimental treatments such as creatine supplementation, omega-3 fatty acids, microRNAs, and antioxidant supplements in addition to physical exercise     

氧化应激与妊娠

氧化应激是指活性氧生成与抗氧化防御系统之间的不平衡状态。氧化应激可在活性氧生成超过抗氧化防御系统时或者在抗氧化剂活性降低时发生。近年来,氧化应激作为多种疾病的发病原因而备受关注。在产科,许多研究表明氧化应激和妊娠有关。     

Resources and Biological Activities of Natural Polyphenols

The oxidative stress imposed by reactive oxygen species (ROS) plays an important role in many chronic and degenerative diseases. As an important category of phytochemicals, phenolic compounds universally exist in plants, and have been considered to have high antioxidant ability and free radical scavenging capacity, with the mechanism of inhibiting the enzymes responsible for ROS production and reducing highly oxidized ROS. Therefore, phenolic compounds have attracted increasing attention as potential agents for preventing and treating many oxidative stress-related diseases, such as cardiovascular diseases, cancer, ageing, diabetes mellitus and neurodegenerative diseases. This review summarizes current knowledge of natural polyphenols, including resource, bioactivities, bioavailability and potential toxicity.     

Antioxidants in the prevention of renal disease

Reactive oxygen species (ROS) play a key role in the pathophysiological processes of renal diseases. The cellular damage is mediated by an alteration in the antioxidant status, which increases the concentration of ROS in the stationary state (oxidative stress). Oxidative stress mediates a wide range of renal impairments, from acute renal failure, rhabdomyolysis, obstructive nephropathy, hyperlipidemia, and glomerular damage to chronic renal failure and hemodialysis. Therefore, interventions favoring the scavenging and/or depuration of ROS (dietary and pharmacological antioxidants) should attenuate or prevent the oxidative stress, thereby mitigating against the subsequent renal damage.     

Oxidative stress-induced biomarkers for stem cell-based chemical screening

Stem cells have been considered for their potential in pharmaceutical research, as well as for stem cell-based therapy for many diseases. Despite the potential for their use, the challenge remains to examine the safety and efficacy of stem cells for their use in therapies. Recently, oxidative stress has been strongly implicated in the functional regulation of cell behavior of stem cells. Therefore, development of rapid and sensitive biomarkers, related to oxidative stress is of growing importance in stem cell-based therapies for treating various diseases. Since stem cells have been implicated as targets for carcinogenesis and might be the origin of “cancer stem cells”, understanding of how oxidative stress-induced signaling, known to be involved in the carcinogenic process could lead to potential screening of cancer chemopreventive and chemotherapeutic agents. An evaluation of antioxidant states reducing equivalents like GSH and superoxide dismutase (SOD), as well as reactive oxygen species (ROS) and nitric oxide (NO) generation, can be effective markers in stem cell-based therapies. In addition, oxidative adducts, such as 4-hydroxynonenal, can be reliable markers to detect cellular changes during self-renewal and differentiation of stem cells. This review highlights the biomarker development to monitor oxidative stress response for stem cell-based chemical screening.     

Flavonoids: antioxidants against atherosclerosis

Oxidative stress results from an imbalance between excessive formation of reactive oxygen species (ROS) and/or reactive nitrogen species and limited antioxidant defences. Endothelium and nitric oxide (NO) are key regulators of vascular health. NO bioavailability is modulated by ROS that degrade NO, uncouple NO synthase, and inhibit synthesis. Cardiovascular risk conditions contribute to oxidative stress, causing an imbalance between NO and ROS, with a relative decrease in NO bioavailability. Dietary flavonoids represent a range of polyphenolic compounds naturally occurring in plant foods. Flavonoids are potentially involved in cardiovascular prevention mainly by decreasing oxidative stress and increasing NO bioavailability.     

Brain rust: recent discoveries on the role of oxidative stress in neurodegenerative diseases

Oxidative stress (OS) and damages due to excessive reactive oxygen species (ROS) are common causes of injuries to cells and organisms. The prevalence of neurodegenerative diseases (ND) increases with aging and much of the research involving ROS and OS has emerged from works in this field. This text reviews some recent published articles about the role of OS in ND. Since there are many reviews in this field, the focus was centered in articles published recently. The Scientific Journals Directory supported by the Brazilian Ministry of Education Office for the Coordination of Higher Educational Personnel Improvement (CAPES) was used to search, download, and review articles. The search engine looked for the terms 'oxidative stress AND neurodegenerative diseases AND nutrition' in 10 different scientific collections. Biochemical markers for ND lack sensitivity or specificity for diagnosis or for tracking response to therapy today. OS has an intimate connection with ND, albeit low levels of ROS seem to protect the brain. Deleterious changes in mitochondria, OS, calcium, glucocorticoids, inflammation, trace metals, insulin, cell cycle, protein aggregation, and hundreds to thousands of genes occur in ND. The interaction of genes with their environment, may explain ND. Although OS has received much attention over the years, which increased the number of scientific works on antioxidant interventions, no one knows how to stop or delay ND at present. Interventions in vitro, in vivo, and in humans will continue to contribute for a better understanding of these pathologies.