慢性乙型肝炎患者氧化损伤的研究

目的　探讨慢性乙型肝炎 (乙肝 )患者体内氧化损伤的情况。方法　检测 30例慢性乙肝患者氧化损伤指标 (丙二醛、总抗氧化能力、抗坏血酸 )、肝功能、乙型肝炎病毒 (HBVDNA) ,并做出统计分析。结果　慢性乙肝患者组与正常对照组比较 :丙二醛浓度明显升高 (P <0 0 5 ) ;ALT正常组与正常对照组比较 :抗坏血酸血清浓度明显升高 (P <0 0 1) ;ALT异常组与正常对照组及ALT正常组比较 :丙二醛血清浓度均明显升高 (P <0 0 5 )。在慢性乙型肝炎患者中 ,丙二醛浓度与ALT水平呈明显正相关 (r=0 6 1) ,抗坏血酸浓度与ALT水平呈明显负相关 (r =- 0 6 4 )。乙肝HBVDNA与抗氧化指标间无联系 (P >0 0 5 )。总抗氧化能力指标在各组间比较均无明显改变。结论　乙肝患者体内有氧化 抗氧化功能障碍。慢性乙肝患者ALT升高时 ,体内氧化损伤程度加重。慢性乙型肝炎患者ALT正常者 ,体内氧化损伤程度不高。氧化损伤指标与HBVDNA是肝炎患者中相对独立的检查指标。     

慢性丙型肝炎患者氧化损伤的研究

目的 探讨慢性丙型肝炎(CHC)患者体内氧化损伤的情况.方法 52例CHC患者,按丙氨酸转氨酶(ALT)水平分为A组(ALT上升组)和B组(ALT正常组).正常对照组为20例健康志愿者.利用酶联免疫吸附法(ELISA)测定研究对象血清黄嘌呤氧化酶(XOD),丙二醛(MDA),氧化型谷胱甘肽(GSSG),谷胱甘肽(GSH),谷胱甘肽过氧化物酶(GSH-Px),谷胱甘肽巯基转移酶(GST),谷胱甘肽还原酶(GR)及维生素C(Vc)水平,并作出统计分析.结果 CHC患者血清XOD,MDA,GST和GR水平较正常对照组显著升高,而GSH,GSH-Px和Vc水平则明显降低.同时,A组患者血清XOD,MDA,GSSG,GST及GR水平较B组患者显著上调,而GSH,GSH-Px和Vc水平则显著下调.在CHC患者中,血清XOD,MDA,GSSG,GST水平与ALT水平呈正相关,血清GSH,GSH-Px,Vc与ALT水平呈负相关;血清XOD,MDA,GSSG,GR,GST水平与AST水平呈正相关,血清GSH-Px水平与AST水平呈负相关;血清GR水平与GGT水平呈正相关,血清GSH水平与GGT水平呈负相关;血清MDA,GR水平与AKP水平呈正相关.在CHC组中,仅血清XOD水平与血清HCV RNA水平间存在正相关关系.结论 CHC患者体内存在一定程度的氧化损伤,随血清ALT水平的升高,机体氧化损伤程度进一步加重.     

石英粉尘与DNA的氧化损伤

石英粉尘广泛存在于采矿、掘进、玻璃制造、陶瓷工业等生产环境当中 ,它对人体的各种损害作用倍受广泛关注。研究表明 ,石英粉尘通过相关的自由基 (free radicals,FR)的介导 ,可对膜蛋白质、膜脂质、糖类、DNA分子等产生广泛的损伤作用 ,引起以矽肺、肺癌为主的一系列临床疾病。本文就石英粉尘的 DNA损伤作用作一概述。1　石英粉尘与自由基自由基是指含有一个或一个以上不成对电子的任何分子或离子 ,主要由化合物中共价键的均裂所致 ,具有极强的反应性。研究表明 ,石英粉尘的毒作用主要由自由基介导 ,与石英粉尘的毒作用有关的自由基主…     

线粒体DNA氧化损伤与肿瘤发生

线粒体DNA(mitochondrial DNA,mtDNA)是哺乳动物细胞内唯一的核外遗传物质。1981年Ander-son等首次在《Nature》上公布了人类mtDNA基因组的全部核苷酸序列,并绘制了详细的功能图谱。每个细胞内含有数个到上万个不等的线粒体,而每个线粒体内含有数个到数十个不等的mtDNA分子。研     

COX-2抑制剂通过非COX依赖性途径对抗心肌氧化损伤

目的： 研究环加氧酶2（COX-2）抑制剂尼美舒利和COX-1抑制剂比罗昔康在对抗心肌氧化应激损伤中的作用及其机制。方法: 离体大鼠心脏行Langendorff灌流，分别给予H₂O₂、pyrogallol（可产生超氧阴离子）或Vit C+Fe2+（可产生羟自由基），观察心脏收缩功能、心肌LDH和MDA含量。心肌COX的活性用PGI₂的稳定产物6-Keto-PGF_1α的含量表示。结果: 尼美舒利（3 mg/kg）可明显减轻H₂O₂引起的收缩功能下降（10 min 应激时LVDP为72%±10% vs 61%±11%，P<0.05），减少LDH释放［（5.5±2.5）U/L vs （8.0±2.1）U/L，P<0.05）］。而比罗昔康（3 mg/kg）虽然能抑制H2O2应激时LVDP的下降（73%±10% vs 61%±11%，P<0.05），却加重LVEDP的上抬［（29.00±5.61）mmHg vs（23.16±3.57） mmHg，P<0.01］。尼美舒利亦能减轻超氧阴离子和羟自由基引起的心肌损伤作用。尼美舒利和比罗昔康预处理对H₂O₂应激心肌6-Keto-PGF_1α含量无明显影响。线粒体ATP敏感性钾通道（mitochondrial ATP sensitive potassium channel，mitoK_ATP）的阻断剂5-HD可取消尼美舒利减轻H₂O₂引起的LVDP和±dp/dt_max降低作用（分别为53%±12% vs 69%±3%、58%±11% vs 72%±7%和37%±8% vs 51%±4%，P<0.01）。结论: COX-2抑制剂尼美舒利可以对抗心肌氧化损伤，其机制通过非COX依赖性途径发挥作用，而mitoK_ATP可能参与尼美舒利的保护作用。     

全血贮存期间氧化损伤及抗氧化系统的变化

目的：探讨４℃条件下保存对血液氧化与抗氧化反应的影响。方法：采用化学比色法检测血浆丙二醛（ＭＤＡ）含量,血浆总氧抗氧化活性（ＡＯＡ）和红细胞超氧化物歧化酶（ＳＯＤ）活力。结果：血液在４℃保存时,随贮存时间的延长,血浆ＭＤＡ含量逐渐增加（Ｐ＜００５,Ｐ＜００１）,血浆总抗化活性和红细胞ＳＯＤ活力逐渐降低,（Ｐ＜００５,Ｐ＜００１）。２１ｄ后红细胞膜的流动性明显降低（Ｐ＜００５,Ｐ＜００１）。结论：全血贮存过程中的氧化损伤,除与自由基在膜上发生过氧化反应作用外,还与抗氧化系统障碍有关。     

胃癌患者血浆氧化抗氧化状态及组织8-羟基鸟嘌呤糖苷酶mRNA表达水平

目的:探讨胃癌患者体内氧化及抗氧化水平的变化与胃癌的关系。方法:以胃腺癌患者(n=48)和健康人(n=30)空腹外周血为标本,采用紫外分光光度法检测氧化酶指标(MPO、XOD)、总抗氧化能力(T-AOC)以及丙二醛(MDA)的表达水平,采用酶联免疫吸附法(ELISA)测定8-羟基鸟嘌呤(8-OHdG)的表达。采用荧光定量RT-PCR法测定胃腺癌组织(n=68)和正常组织(n=12)中8-羟基鸟嘌呤糖苷酶mRNA表达水平。结果:胃癌组血浆XOD、MPO表达水平分别为(10.46±7.23)U/L、(23.71±25.06)U/L,健康对照组血浆XOD、MPO表达水平分别为(5.85±2.27)、(5.16±11.35)U/L,胃癌组均高于对照组,差异具有统计学意义(P<0.05);胃癌组T-AOC的表达水平为(5.02±3.13)U/mL,健康对照组为(19.40±7.18)U/mL,胃癌组低于对照组(P<0.05);胃癌组血浆8-OHdG和MDA的表达水平分别为(14.76±12.41)ng/mL、(18.83±4.19)nmol/mL,健康对照组为(6.49±5.75)ng/mL、(7.11±6.20)nmol/mL,胃癌组高于对照组(P<0.05)。胃癌组织中hOGG1 mRNA相对表达值(5.34±2.37)高于对照组的表达(1.04±0.76),差异有统计学意义(Z=1.964,P<0.05)。结论:胃腺癌患者体内氧化应激水平升高以及抗氧化防御水平的降低,胃腺癌组织中hOGG1mRNA表达增强。     

着色性干皮病与DNA损伤修复

着色性干皮病是一种常染色体隐性遗传病，有七组互补型和一种变异型，该病的发生与DNA的损伤修复缺陷有关，本拟对着色性干皮病基因的克隆，在DNA损伤修复中的作用以及与肿瘤的关系等方面的进展作一综述。     

山稔子提取物对体外DNA氧化性损伤的保护作用

目的观察山稔子提取物对原代体外培养淋巴细胞DNA氧化损伤的保护作用。方法原代培养24h的脾淋巴细胞悬液,随机分为7组,其中5组细胞用不同浓度的山稔子提取物溶液预先处理60min,再加入50μmol/L的H2O2,H2O2染毒组直接加入相同浓度的H2O2,空白对照组加入等量的PBS溶液,7组细胞共同在4℃下染毒20min,收获细胞同时进行单细胞凝胶电泳,计算DNA迁移的细胞率和总彗星长度。结果H2O2可致原代培养脾淋巴细胞的DNA严重损伤,而山稔子提取物能不同程度地降低H2O2诱导产生的DNA损伤,在10、50、100μg/mL的浓度下,彗星细胞出现率从阳性对照组的100%分别降低为85%、65%和30%（P分别〈0.05、0.01、0.01）,总彗星长度也从对照组的（52.82±6.42）μm,逐渐降低为（43.68±5.59）μm、（35.80±8.75）μm、（25.35±4.32）μm（P分别〈0.05、0.01、0.01）。结论山稔子提取物具有抗氧化作用,能在一定浓度范围内保护细胞显著降低氧自由基对DNA的氧化损伤。     

内源性硫化氢调节慢性阻塞性肺疾病大鼠氧化/抗氧化平衡

目的: 探讨硫化氢(H₂S)在吸烟(CS)联合脂多糖(LPS)建立的大鼠慢性阻塞性肺疾病(COPD)模型中的抗氧化作用。方法: 32只清洁级健康雄性SD (Sprague-Dawley)大鼠,随机分为4组:对照组(control)、CS+LPS组、CS+LPS+硫氢化钠(NaHS,H₂S供体)组、CS+LPS+炔丙基甘氨酸(PPG,胱硫醚-γ-裂解酶抑制剂)组。30 d后测定大鼠肺功能,光镜观察肺组织病理变化并予评分;测定血浆中H₂S含量及肺组织中胱硫醚-γ-裂解酶(CSE)蛋白表达;检测肺组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)及过氧化氢酶(CAT)活性以反映氧化应激。结果: 与对照组相比,CS+LPS组大鼠呼气峰流速(PEF)下降24%(P<0.01),气道内压(IP)升高66%(P<0.01),肺组织病理评分升高(P<0.01);NaHS或PPG干预后,与CS+LPS组比较,肺功能无改变;NaHS干预后,病理评分下降(P<0.05)。在第16 d时,CS+LPS组血浆中H₂S含量较对照组升高26%(P<0.05);30 d后,CS+LPS+PPG组较CS+LPS组H₂S含量降低22%(P<0.01)。CS+LPS组中CSE蛋白表达较对照组升高(P<0.01);与CS+LPS组比较,CS+LPS+NaHS组和CS+LPS+PPG组无显著差异。与对照组相比,CS+LPS组肺组织中MDA含量升高24%(P<0.05),总SOD活性升高47%(P<0.01),CAT活性升高52%(P<0.01);与CS+LPS组相比,NaHS干预后, MDA含量降低21%(P<0.05),总SOD活性及CAT活性无显著差异;而PPG干预后,总SOD活性下降33%(P<0.05)。结论: H₂S在COPD大鼠中起到抗氧化作用,CSE/H₂S途径可能参与COPD疾病的发展。     

Oxidative stress and endothelial damage in patients with asymptomatic carotid atherosclerosis

It is know that oxidative stress can be able to induce cytotoxicity of blood cells, stimulate release of inflammatory cytokines, and induce the production of growth factors. The aim of this study was to investigate oxidative stress and endothelial dysfunction in patients with asymptomatic carotid artery disease and healthy controls. Native low-density lipoproteins, oxidised low-density lipoproteins, malondialdehyde, nitrates, glutathione peroxidase activity and endothelin-1 were determined in patients without severe (range between 30% and 50%) carotid artery stenosis. Native low-density lipoproteins, oxidized low-density lipoproteins, malondialdehyde, glutathione peroxydase, and endothelin-1 concentrations were higher in patients than in health controls (P<0.001). No difference was observed in nitrate values (P<0.8). Our results revealed oxidative stress in patients without severe carotid artery stenosis and clinical symptoms. This was shown by the elevated malondialdehyde and oxidized low-density lipoprotein levels. Received: 6 July 2000 / Accepted: 2 February 2001     

DNA base excision repair activities in mouse models of Alzheimer's disease

Alzheimer's disease (AD) has been correlated with elevated levels of oxidative DNA damage. Base excision repair (BER) is the main repair pathway for the removal of oxidative DNA base modifications. We have recently found significant functional deficiencies in BER in brains of sporadic AD and amnestic mild cognitive impairment patients. In this study we tested whether altered BER activities are associated with appearance of symptoms in different brain regions of pre-symptomatic and symptomatic mice harboring mutant APP alone or in combination with Tau and PS1. Our results suggest that unlike in humans, the development of AD-like pathology in the studied mouse models is not associated with deficiencies in BER.     

Graves'病患者血清骨钙素测定及临床意义

目的：探讨Graves’病患者血清骨钙素（BGP）水平变化特点及临床意义。方法：对158例Graves’病患者血清BGP水平进行分析，并与甲状腺功能主要指标（T3、T4、FT3、FT4、TSH、TGA、TMA）进行相关分析。结果：Graves’病患者血清BGP水平明显高于正常对照组；Graves’病患者血清BGP水平与T3、T4、FT3、FT4呈正相关，而与TSH、TGA、TMA无明显相关。结论：血清BGP可作为监测Graves’病患者骨代谢状况及Graves’病骨病发生的重要指标之一。     

弥漫性毒性甲状腺肿患者瘦素水平及临床意义

目的：探讨弥漫性毒性甲状腺肿对人体血清瘦素水平的影响。方法：选取弥漫性毒性甲状腺肿患者51例,并以甲减组、正常组为对照,应用免疫放射分析（IRMA）测定血清瘦素水平,并测甲功,计算体重指数（BMI）和体脂百分数（%Fat）。结果：弥漫性毒性甲状腺肿患者瘦素水平（男性2.05±1.54μg/L,女性7.47±5.08μg/L）显著低于正常组,而且扣除体脂因素后仍很明显（P〈0.01）。甲减组瘦素水平与正常组相比显著升高,但排除体脂因素后,两组差异无显著性。三组瘦素水平均与BMI显著正相关,与游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）呈弱负相关,与促甲状腺激素（TSH）呈弱正相关,但无统计学意义。各组中女性瘦素水平均为男性的（2-3）倍。结论：甲功改变通过体脂含量间接影响瘦素水平。     

广西地区壮族Graves病与CTLA4基因多态性相关性研究

目的分析CTLA4基因微卫星多态性与广西地区壮族Graves病（Graves’disease，GD）相关性。方法提取48例广西地区壮族GD患者和44名正常对照组的外周血白细胞基因组DNA，应用聚合酶链反应检测CTLA4第4外显子的3’非翻译区包含（AT）n[CTLA4（AT）n]重复序列的特异性等位基因。结果广西地区壮族人CTLA4微卫星多态性检出19种等位基因。壮族GD组106bp等位基因频率与正常对照组比较显著增高，差异有统计学意义（P〈0．05）。结论广西壮族GD患者与CTLA4基因多态性明显相关,CTA4（AT）n 106bp可能是广西壮族GD的易感等位基因。     

Diabetes and chronic nitrate therapy as co-determinants of somatic DNA damage in patients with coronary artery disease

Somatic DNA damage has been linked to coronary artery disease (CAD). However, whether genetic instability is linked to CAD per se or to concomitant potentially genotoxic metabolic and pharmacological factors remains still unclear. The aim of this study was to evaluate the determinants of somatic DNA damage in a large population of patients undergoing coronary angiography. A total of 278 in-hospital patients (215 men, age 61.8±0.7 years) were studied by using micronucleus assay (MN) in human lymphocytes, which is one of the most commonly used biomarker for somatic DNA damage. Significant CAD (>50% diameter stenosis) was present in 210 patients (179 men, age 62.3±0.7 years). Normal coronary arteries were observed in 68 patients (35 men, age 60.2±1.7 years). There were no significant differences between patients with and without CAD, but patients with multivessel disease had the highest MN levels (P=0.01). MN frequency was also found significantly higher in presence of type 2 diabetes (P<0.0001), dyslipidemia (P=0.048) and nitrate therapy (P=0.0002). A significant additive effect was also observed between diabetes and nitrate therapy (P=0.02). On multivariate logistic regression analysis, diabetes [odds ratio =6.8 (95% confidence interval, 3.2–14.5), P<0.0001] and nitrate therapy [odds ratio =2.4 (95% confidence interval, 1.3–4.7), P=0.01] remained the only significant determinants for the 50th percentile of MN (>12). These results indicated that diabetes and, to a lesser extent, chronic nitrate therapy are major determinants of somatic DNA instability in patients with CAD. DNA damage might represent an additional pathogenetic dimension and a possible therapeutic target in the still challenging management of coronary artery disease concerning diabetics.     

不同临床期Graves''病患者外周血分泌TRAb前体细胞频率的差异

目的：探讨分泌TRAb的前体细胞频率与Graves‘病临床分期的关系。方法：利用EB病毒体外激活外周血淋巴细胞，测定不同临床期GD患者外周血中潜在的TRAb分泌细胞的频率差异。结果：血清TRAb较高的初发和复发期患者的分泌TRAb的转化B细胞阳性孔占免疫球蛋白阳性孔的百分率远高于正常对照，2例初发病人的阳性率分别为34．6％和29．1％，1例复发病人阳性率为30％，正常对照中也可以检出较低频率的TRAb前体细胞，2例血清TRAb阴性的缓解期病人的外周血中，其中1例分泌TRAb前体细胞频率（5．3％）与正常无差异，另1例TRAb前体细胞频率（10．7％）高于正常对照。EBV转化的TRAb前体细胞以分泌IgM型抗体为主。结论：不同临床期的Graves‘病患者的外周血中分泌TRAb的前体细胞的频率不同。     

Oxidative stress and DNA damage induced by spinosad exposure in Spodoptera frugiperda Sf9 cells

Spinosad, a neurotoxic insecticide, is widely used for crop protection. In order to elucidate the effects of spinosad on oxidative stress and genotoxicity in Sf9 cells, the levels of lipid peroxidation, the activity of antioxidative enzymes, and DNA damage were measured. The results showed that spinosad caused a time-dependent increase in the formation of malondialdehyde and decrease in the activity of superoxide dismutase and catalase. Further studies confirmed that spinosad induced 8-oxoguanine accumulation in Sf9 cells, which is accompanied by increased expression of DNA repair enzymes (OGG1 and MTH1). The neutral comet assay revealed that spinosad induced significant time-related increases of DNA double-strand breaks in Sf9 cells. Our results indicate that spinosad effectively induced oxidative stress and DNA damage in Sf9 cells.     

Immunogenetic markers in patients with Graves' disease

Summary 110 carefully characterized Caucasoid patients with Graves' disease were tested for HLA class I and class II antigens. Compared with Caucasian controls (n=193), the frequencies of HLA B8, Cw7 and DR3 were significantly increased (p_c<0.05). In the subgroups with and without exophthalmos, HLA A3 exhibited a negative but insignificant association with the eye involvement, while A19 and Cw2 showed positive, however even weaker correlations with eye disease. HLA DR5 was associated with relapsing thyrotoxicosis, whereas HLA DR7 and B12 were negatively correlated with relapse. These results confirm the positive correlation of HLA B8 and DR3 with Graves' disease and reveal a not yet observed association with Cw7. Reported correlations of antigen frequencies with eye disease and relapsing thyrotoxicosis could not be confirmed. Other previously unknown, however subtle differences in disease subgroups were observed.Abbreviations EF etiologic fraction - HLA Human leukocyte antigens - RR relative risk - TRAb TSH receptor antibodies - TSH Thyroid stimulating hormone