氧自由基清除剂对供心的保护作用

氧自由基损伤是心脏移植中供心缺血再灌注损伤的重要机制,研究表明合理的应用氧自由基清除剂能够减轻这种损伤.对内源性氧自由基清除荆辅酶Q10、别嘌呤醇等及外源性氧自由基清除荆依达拉奉和L-抗坏血酸2-[3,4-二氢-2,5,7,8-四甲基-2-(4,8,12-三甲基十三烷基)-2H-1.苯并吡喃-6-磷酸酯]钾盐等的实验研究显示氧自由基清除剂能够对供心(包括无心跳供体心)起到保护作用.     

应用单细胞凝胶电泳比较研究砷对人类细胞DNA的损伤

目的：探讨不同细胞对砷的基因毒性反应及其机理,探讨快速,敏感及经济的细胞基因毒性检测方法。方法：应用单细胞凝胶电泳（Single cell gel electrophoresis,SCGE)或彗星试验（comet assay)比较研究,结果;细胞DNA损伤与砷处理量间呈显著的剂量反应关系和时效关系。受试细胞对砷的基因毒性反应的敏感性强弱顺序为：PMA－HL60＞DMSO－HL60＞HL60＞淋巴细胞,人工计数彗星尾分级频数与计算机自动测量慧星尾DNA泳动量的结果完全一致,用非参数Mann-Whitney多变量检验分析彗星尾分级频数的显著性与参数Tukey多变量检验分析量彗星尾DNA泳动量的显著性完全相同,而且不同浓度的砷与5级彗星尾频数的相关性比其与阳性彗星尾总数间的更为显著,结论：微量砷即可引起细胞不同程度的DNA损伤,不同细胞亚群对砷的基因毒性反应不同,SCGE是一个简便,快速,敏感及经济的细胞基因毒性检测方法,可应用于各级水平的环境与人类疾病（砷污染）监测与研究。     

氧自由基清除剂对老年人慢性肺心病急性加重期治疗作用的研究

目的探讨氧自由基（ＯＦＲ）清除剂对慢性肺心病的治疗效果及其作用机理。方法对４２例病人（实验组）用抗炎加３种ＯＦＲ清除剂治疗，与３３例病人（对照组）只用抗炎治疗，进行临床随机对照研究。两组病人治疗前后均作ＯＦＲ代谢指标检测，并进行临床综合疗效判断。结果实验组的全血硒含量和谷胱甘肽过氧化物酶活性显著升高，血清丙二醛含量显著降低（Ｐ＜０．０１）；全血超氧化物歧化酶活性上升（Ｐ＜０．０５）。实验组和对照组的临床总有效率分别为９５．２％和８４．８％。结论３种ＯＦＲ清除剂分别在细胞质，生物膜及细胞外共同发挥清除ＯＦＲ的协同作用。不仅可常规用于本病急性加重期的治疗，而且对本病的缓解期和早期的预防意义可能更大。     

砷对DNA的损伤

目前,地方性饮水型和燃煤型砷中毒以成为我国面临的重要的公共卫生问题,但其机制尚不清楚,已知氧化应激是砷中毒的重要发病机制之一.已经证实砷具有致癌性、神经毒性、免疫毒性等,可通过直接损伤DNA使DNA断裂,抑制DNA修复,引起染色体畸变,诱导遗传物质损伤,使一些酶类表达异常,因而,深入研究砷的遗传毒性具有重要意义.     

砷致HeLa细胞基因组DNA损伤的特点

目的 观察砷致HeLa细胞基因组DNA损伤的特点。方法 在彗星实验中应用彗星图像分析系统（KIAS）技术。结果 砷剂量与DNA拖尾细胞比率之间存在明确的剂量效应递增关系，而且给药各组与阴性对照组细胞在拖尾形态上存在较大差异。结论 砷致HeLa细胞基因组DNA的损伤表现出一定的特异性。     

氧自由基诱导鸭乙型肝炎病毒DNA整合及其细胞传代研究

目的探讨氧自由基对鸭乙型肝炎病毒（DHBV）DNA在受感染细胞DNA上整合发生的影响以及整合后DHBVDNA的细胞传代性。方法选择鸡肝癌细胞株—LMHD21-6,在其由单个细胞培养至3×107～5×107个细胞（共23代）的过程中,用低浓度H2O2（10.0μmol/L）作用于细胞;TUNEL法检测细胞DNA链断裂情况;Southernblot技术观察细胞DNA上新的整合型DHBVDNA的发生情况。结果(1)低浓度H2O2（≤10.0μmol/L）导致的细胞死亡率仅为32.0%,但可诱导细胞DNA链断裂致细胞调亡,而H2O2浓度＞10.0μmol/L时其细胞死亡率＞50.0%;(2)低浓度H2O2作用的细胞DNA上新的DHBVDNA整合发生率为50.0%（6/12）,而无H2O2作用的发生率仅8.33%（1/12）,两者比较差异有显著意义（P＜0.05＝;(3)含新的整合型DHBADNA的细胞在无H2O2作用下,再由单个细胞培养至第23代,其子代细胞DNA上可见与其母代细胞DNA上新的整合型DHBVDNA碱基大小完全一致的DHBVDNA带。结论氧自由基为DHBVDNA整合发生的重要诱因之一,新的整合型DHBVDNA可有较稳定的细胞传代。     

砷对细胞及细胞膜损伤的研究概况

砷是自然界中广泛存在的一种化学元素．是地球200多种矿物质中的主要成分之一。居住于特定地理环境下的居民通过长期摄入饮水、空气或（和）食物中过高的砷而引起以皮肤损害为主的全身性慢性中毒。长期摄入无机砷（〉500μg/d）还可引起心血管系统、神经系统和肝肾功能的改变，也与糖尿病、皮肤癌、膀胱癌、肺癌及前列腺癌的发生有关。     

氧自由基在酒精性胃粘膜损伤中的作用及疏基化合物的保护作用

酒精性胃粘膜损伤时伴有氧自由基水平升高，引起粘膜微循环障碍、细胞膜流动性降低及还原型谷胱甘肽含量减少，巯基化合物可防治酒精性胃粘膜损伤，是机体重要的抗氧化因子。     

砷对神经系统损伤的研究进展

砷（As）是人体非必需元素，经呼吸道、消化道和皮肤与人体接触，当摄入超过排泄．即在人体内蓄积，引起慢性砷中毒．潜伏期几年至几十年。慢性地方性砷中毒可致消化系统、神经系统和皮肤病变．并与多系统癌症有关。由于神经系统具有神经细胞不能再生及其对毒物的毒性作用较其他组织系统更为敏感的特殊性．使之在地方性砷中毒的研究中显得尤为重要。作者仅就慢性砷中毒对神经系统损伤的研究进展综述如下。[第一段]     

衰老对硝酸酯类药物引起活性氮介质和活性氧介质增高的影响

目的:以往研究显示,硝酸酯类药物和衰老都会引发体内活性氧介质(ROS)和活性氮介质(RNS)的增加,本研究旨在探讨年龄是否会影响硝酸酯类药物的这种促进作用。方法:75例不稳定心绞痛患者,分成32例中年组和43例老年两组。所有患者均给予硝酸酯类药物(50μg/min)48h。在试验开始时和用药48小时时,获取血样标本,对血样中的ROS[丙二醛(MDA),髓过氧化物酶(MPO)和还原性谷胱甘肽(GSH)]和RNS(硝基、亚硝基,NOX;过氧亚硝酸阴离子,ONOO-)]的水平进行检测。结果:硝酸酯类药物的使用,引起中年组血浆MDA水平[用药前(1.22±0.37)nmol/m L,用药后(1.61±0.47)nmol/m L,P0.05]增加60%;老年组MDA水平[用药前(2.07±0.77)nmol/m L,用药后(4.05±0.80)nmol/m L,P0.05],增加140%;GSH两组分别减少了9%和48%;硝酸酯类药物使用前,老年组血浆硝基化酪氨酸(398.29±117.0)nmol/L水平为仅为中年组(296.57±120.48)nmol/L的105%,药物使用48h后,老年组血浆硝基化酪氨酸水平(1 182.30±295.01)nmol/L增高到中年组(610.82±217.36)nmol/L,增高210%。结论:在硝酸酯类药物的使用过程中,除了药物本身增加机体内ROS和RNS,年龄增加能够促进硝酸酯类药物的这种作用。     

Generation of reactive oxygen species is not involved in idarubicin-induced apoptosis in human leukaemic cells

The anthracycline antibiotic idarubicin (IDA) induces double-stranded DNA breaks, the generation of reactive oxygen species (ROS) and apoptosis in human leukaemic cells. It is unclear whether the generation of ROS is associated with the apoptotic process. Using the T-lymphoblastic leukaemic CEM cell line, we found that IDA-induced DNA breaks were correlated with final cell death. The reduction in mitochondrial membrane potential (Deltapsim) and the generation of ROS occurred simultaneously with IDA-induced activation of caspase-9 and caspase-3. Inhibition of caspases by a pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk) completely blocked IDA-induced reduction of Deltapsim, apoptosis and final cell death. Interestingly, ROS generation was significantly enhanced by Z-VAD-fmk. ROS generation was neither caspase dependent nor part of the apoptotic process. IDA-mediated reduction in Deltapsim is caspase dependent and is not a consequence of the generation of ROS. These results indicate that IDA-induced generation of ROS and apoptosis are separate events. Inhibition of caspases facilitates IDA-mediated generation of ROS.     

食管癌、胃癌细胞对氧化砷促凋亡的敏感性与固有活性氧水平有关

目的 探讨食管癌，胃癌细胞的固有活性氧（reactive oxygen species,ROS)水平与细胞对三氧化二砷（As2O3)促凋亡敏感性之间的关系。方法 用小剂量（2μmol/L)As2O3作用于人胃癌细胞和食管癌细胞株各一对（SGC7901、MKN45和EC/CUHK1、EC1867），证实As2O3促凋亡敏感性在SGC7901和MKN45之间及EC/CUHK1和EC1867之间均有差异。然后在不加As2O3的情况下，用活性氧捕获剂双氢罗丹明123（DHR123）卵育细胞（DHR123在细胞内被ROS氧化为发出荧光的罗丹明123），通过流式细胞仪检测细胞内罗丹明123的荧光而测得细胞内固有ROS水平。结果 对As2O3敏感的SGC7901细胞的固有活性氧水平比As2O3不敏感的MKN45细胞高，对As2O3敏感的EC/CUHK1细胞的固有活性氧水平比As2O3不敏感的EC1867细胞高。结论 食管癌，胃癌细胞固有ROS水平的差异与细胞对As2O3诱导凋亡的敏感性差异有关。     

雌激素与活性氧

大量证据表明活性氧(ROS)对心脑血管疾病的发生和发展有重要影响。它可以直接氧化膜脂质和DNA,造成细胞氧化损伤和异常;同时还作为信使参与细胞各种生理和病理活动,例如调节基因表达和信号转导。近几年,雌激素对心脑血管疾病的保护作用越来越受到人们的重视,它主要参与细胞内的氧化应激反应,但在某些方面也存在争议。     

凝血酶引起人支气管上皮细胞内活性氧及血小板源生长因子-AB分泌的改变

目的 探讨凝血酶对永生化人支气管上皮细胞(BEP2D细胞)内活性氧产生及血小板源生长因子-AB(PDGF-AB)分泌的影响.方法 不同浓度凝血酶刺激指数生长期的BEP2D细胞,通过检测氧化型氢化乙啶及二氯荧光素荧光强度测定活性氧簇含量变化.采用双抗体夹心ELISA法检测BEP2D细胞分泌PDGF-AB的变化.结果 随着凝血酶浓度增加,反应体系中活性氧明显升高,且有明显的剂量反应关系.凝血酶处理组BEP2D细胞上清液中PDGF-AB含量较对照组上清液显著升高[(770.33+24.29)ng/L vs(117.42±10.85)ng/L,P＜0.01].凝血酶在一定范围内有剂量反应关系.10 U/ml凝血酶刺激48 h后BEP2D细胞分泌PDGF-AB量最大[(817.63+22.53)ng/L].结论 凝血酶既可以引起细胞内氧化应激导致基因毒性,又可以通过刺激BEP2D细胞分泌PDGF-AB发挥自分泌及旁分泌作用.

Abstract：

Objective To investigate the effects of thrombin on reactive oxygen species and plateletderived growth factor-AB (PDGF-AB) in immortalized human bronchial epithelial cells (BEP2D cells).Methods BEP2D cells at exponential growth phase were stimulated by different concentrations of thrombin. The content of active oxygen species was determined by detecting the fluorescence intensity of hydroxyethidium and dichlorofluorescein. The changes of PDGF-AB were measured by double antibody sandwich ELISA assay. Results With the increase of the thrombin concentration, reactive oxygen species significantly increased, and there was a dose-response relationship. The concentration of PDGF-AB in culture supematants in thrombin-treated group was higher than that in control group [(770. 33 +24. 29 )ng/L vs (117. 42+ 10.85) ng/L, P ＜ 0. 01], and there was a dose-response relationship. The concentration of PDGF-AB was maximal [(817.63 +22.53) ng/L] when BEP2D cells were stimulated with 10 U/ml thrombin for 48 hours. Conclusions Thrombin can induce cellular oxidative stress to lead to genotoxicity,and play autocrine and paracrine role by stimulating the secretion of PDGF-AB in BEP2D cells.     

凝血酶引起人支气管上皮细胞内活性氧及血小板源生长因子-AB分泌的改变

目的探讨凝血酶对永生化人支气管上皮细胞（BEP2D细胞）内活性氧产生及血小板源生长因子-AB（PDGF-AB）分泌的影响。方法不同浓度凝血酶刺激指数生长期的BEP2D细胞,通过检测氧化型氢化乙啶及二氯荧光素荧光强度测定活性氧簇含量变化。采用双抗体夹心ELISA法检测BEP2D细胞分泌PDGF-AB的变化。结果随着凝血酶浓度增加,反应体系中活性氧明显升高,且有明显的剂量反应关系。凝血酶处理组BEP2D细胞上清液中PDGF-AB含量较对照组上清液显著升高[（770.33＋24.29）ng/L vs（117.42±10.85）ng/L,P〈0.01]。凝血酶在一定范围内有剂量反应关系。10 U/ml凝血酶刺激48 h后BEP2D细胞分泌PDGF-AB量最大[（817.63＋22.53）ng/L]。结论凝血酶既可以引起细胞内氧化应激导致基因毒性,又可以通过刺激BEP2D细胞分泌PDGF-AB发挥自分泌及旁分泌作用。     

活性氧簇在低氧诱导的肺纤维化中的作用

活性氧簇是一类氧的衍生分子,因其可引起蛋白质、DNA等大分子物质损伤、脂质过氧化,一直被认为是有害因子.近年来研究表明活性氧簇的产生是受精细调节的,并且它能作为第二信使激活细胞内MAPK(ERK1/2、p38MAPK和JNK)、Akt/PKB、JAK-STAT、核因子κB等多条信号通路,参与转化生长因子β1、血小板衍生生长因子、缺氧诱导因子、结缔组织生长因子等多种致纤维化因子的信号转导,调节细胞的增殖、分化、凋亡等生理功能,并与动脉粥样硬化、肝纤维化、肺纤维化等疾病的发生有关.低氧是一个重要的病理过程,可引起细胞损伤、组织炎细胞浸润,并能促进上皮细胞向间质细胞转化、细胞外基质沉积,上调转化生长因子β1、血小板衍生生长因子、缺氧诱导因子、结缔组织生长因子等多种致纤维化因子,故低氧有诱导肺纤维化形成的可能.而低氧又可引起活性氧簇产生增多.本文就活性氧簇在低氧诱导的肺纤维化中的作用作一综述.     

Influence of dichloromethylene diphosphonate on reactive oxygen species production by human neutrophils

Summary Biphosphonates suppress bone destruction in various diseases. Several studies have demonstrated the potential use of biphosphonates in arthritis. The results of these studies indicate that the effectiveness of the biphosphonates, for inhibiting the arthritic process, is related to their antiresorptive properties. It has been shown that the generation of reactive oxygen species is associated with the formation of new osteoclasts and enhanced bone resorption. We studied the effects of the dichloromethylene diphosphonate on the reactive oxygen species production by activated polymorphonuclear leucocytes, measured by chemiluminescence. Our results indicate a dose-dependent inhibitory effect of dichloromethylene diphosphonate on reactive oxygen species production by polymorphonuclear leucocytes stimulated with N-formil-methionyl-leucyl-phenylalanine, the calcium ionophore A23187 and phorbol myristate acetate. The mechanisms by which this biphosphonate inhibits the reactive oxygen species production by activated polymorphonuclear leucocytes are discussed.     

Inflammation and reactive oxygen species in cardiovascular disease

Reactive oxygen species (ROS) have long been proposed to be mediators of experimental cardiovascular pathology. There is also a wealth of data indicating that ROS are involved in clinical cardiovascular pathology. However, multiple clinical studies have shown little benefit from anti-oxidant treatments, whereas nearly all experimental studies have shown a marked effect of anti-oxidant therapy. One reason for this discrepancy is that ROS are produced through multiple different mechanisms of which some are clinically beneficial; thus, in a defined experimental system where predominately pathological ROS are generated does not mimic a clinical setting where there are likely to be multiple ROS generating systems producing beneficial and pathological ROS. Simple inhibition of ROS would not be expected to have the same result in these two situations; ergo, it is important to understand the molecular mechanism underlying the production of ROS so that clinical treatments can be tailored to target the pathological production of ROS. One such example of this in cardiovascular biology is tissue specific inflammation-mediated ROS generation. This and the following series of articles discuss the current understanding of the role of ROS in cardiovascular disease, specifically focusing on the molecular mechanisms of ROS generation and the actions of ROS within the cardiovascular system. Although there are still many areas with regard to the effects of ROS in the cardiovascular system that are not completely understood, there is a wealth of data suggesting that blocking pathological ROS production is likely to have beneficial clinical effects compared to traditional anti-oxidants.     

Nitroglycerine causes mitochondrial reactive oxygen species production: in vitro mechanistic insights

BACKGROUND: Nitroglycerine (GTN) is an organic nitrate that has been used for more than 100 years. Despite its widespread clinical use, several aspects of the pharmacology of GTN remain elusive. In a recent study, the authors of the present study showed that GTN causes opening of the mitochondrial permeability transition pore (mPTP) and mitochondrial production of reactive oxygen species (ROS). OBJECTIVE: In the present study, it was tested whether GTN-induced ROS production depends on mitochondrial potassium ATP-dependent channel or mPTP opening, and/or GTN biotransformation. METHODS AND RESULTS: Isolated rat heart mitochondria were incubated with succinate (a substrate for complex II) and GTN, causing immediate ROS production, as manifested by chemiluminescence. This ROS production was prevented by concomitant vitamin C incubation. Conversely, inhibitors of potassium ATP-dependent channels, mPTP opening or of GTN biotransformation did not modify ROS production. CONCLUSIONS: GTN triggers mitochondrial ROS production independently of the opening of mitochondrial channels and/or of GTN biotransformation. The present data, coupled with previous evidence published by the same authors that GTN causes opening of mPTPs, provide further evidence on the pharmacology of GTN. It is proposed that GTN causes direct uncoupling of the respiratory chain, which determines ROS production and subsequent mPTP opening. The clinical implications of these findings are also discussed.