同型半胱氨酸与氧化应激

2型糖尿病患者多伴有高同型半胱氨酸血症,胰岛素抵抗和同型半胱氨酸与心脑血管疾病以及2型糖尿病患者大、微血管并发症的患病率和病死率相关.同型半胱氨酸在糖尿病各种并发症的发生、发展中起重要作用.糖尿病患者体内氧化应激标志物的水平明显改变,目前认为氧化应激是糖尿病及其各种并发症的发生、发展的共同机制.高同型半胱氨酸引起的氧化应激在糖尿病血管病变、神经病变和胰岛β细胞的损伤中起重要作用.     

同型半胱氨酸在心血管疾病发病中的作用及其机制

同型半胱氨酸(Homocysteinemia,Hcy)是体内蛋氨酸代谢的中间产物,血液中总Hcy的浓度病理性升高导致高同型半胱氨酸血症(Hyperhomocysteinemia．HHcy)。早在1969年,McCully发现由于VitB12的代谢障碍以及VitB6依赖的胱硫醚-β-合酶(cystathionine—β—synthase CBS)缺陷均可导致HHcy并伴有严重动脉粥样硬化的病变,     

同型半胱氨酸诱导THP-1单核细胞产生巨噬细胞炎性蛋白1α

为探讨同型半胱氨酸对人单核细胞表达和分泌巨噬细胞炎性蛋白 1α的影响并检测其活性 ,在体外培养的THP 1单核细胞培养基中加入终浓度为 0 .0 5mmol L、0 .1mmol L和 0 .2mmol L的同型半胱氨酸 ,孵育 8h ,或加入终浓度 0 .1mmol L的同型半胱氨酸 ,分别孵育 4、8及 16h ,用酶联免疫吸附法检测其培养基中的分泌性巨噬细胞炎性蛋白 1α。用改良Boyden小室微孔滤膜法检测THP 1单核细胞条件培养基中巨噬细胞炎性蛋白 1α蛋白对外周血单核细胞的趋化活性。结果发现 ,培养的THP 1单核细胞暴露于不同浓度或同一浓度不同孵育时间的同型半胱氨酸后 ,其分泌至条件培养基中巨噬细胞炎性蛋白 1α蛋白呈浓度和时间依赖性递增 (P <0 .0 1)。趋化实验表明 ,经同型半胱氨酸刺激的THP 1条件培养基引起单核细胞迁移距离 ( 83 .2± 4.8μm)明显大于未经同型半胱氨酸刺激的条件培养基组 ( 73 .2± 2 .3 μm)和随机移动组 ( 62 .4± 3 .5 μm)。方差分析显示 ,三组间均有显著性差异 (F =3 10 .70 ,P <0 .0 1)。在经同型半胱氨酸刺激的THP 1条件培养基中加入巨噬细胞炎性蛋白 1α抗体后 ,单核细胞的移动距离较不含抗体组明显缩短 (P <0 .0 1)。结果提示 ,同型半胱氨酸能诱导THP 1单核细胞表达有趋化活性的分泌性巨噬细胞炎性蛋     

慢性高同型半胱氨酸血症兔的氧化应激损伤

大量的实验证明 ,同型半胱氨酸 (Hcy)是导致动脉粥样硬化的独立的危险因素 ,而其机理认为是氧化应激的作用。本实验旨在探讨 Hcy导致损伤的机理。1　材料和方法1.1　 实验对象　新西兰兔 2 7只 ,雄性 15只 ,雌性 12只 ,体重2 .0～ 2 .5 kg,4～ 5月龄。随机分为对照组 (9只 ,进食正常基础饲料 ) ;蛋氨酸组 (9只 ,正常饲料中每日加蛋氨酸 0 .8g/ kg体重及 2 5 g黄豆粉 ,混匀后进食 ) ;蛋氨酸 +VC组 (9只 ,正常饲料中每日加蛋氨酸 0 .8g/ kg体重、VC1.0 g/ kg体重及 2 5 g黄豆粉 ,混匀后进食 )。1.2 　 实验方法　每只兔于实验前耳缘静脉取…     

同型半胱氨酸对人THP-1巨噬细胞CD36表达的影响

目的:探讨同型半胱氨酸(Hcy)对人THP-1巨噬细胞CD36表达的影响.方法:在应用佛波酯(PMA)诱导分化成功的人THP-1巨噬细胞中加入0、0.01、0.05、0.1、0.2 mmol/L的Hcy孵育24 h(为阴性对照组、0.01 mmol/L Hcy组、0.05 mmol/L Hcy组、0.1 mmol/L Hcy组和0.2 mmo]/L Hcy组);并与0.1 mmol/L Hcy分别培养0、3、6、12、24,48 h,同时以上述各个时点为参照设对照,用流式细胞仪检测THP-1巨噬细胞CD36分子的表达.结果:THP-1巨噬细胞与不同浓度(0、0.01、0.05、0.1、0.2 mmol/L)Hcy孵育24 h后,0.2 mmol/L Hcy组与阴性对照组比较,THP-1巨噬细胞CD36表达增加最明显(P＜0.05),差异有统计学意义.THP-1巨噬细胞与0.1 mmol/L Hcy培养0、3、6、12、24、48 h,各时间点CD36表达均高于其相应的对照(P均＜0.05),差异均有统计学意义;48 h时与0 h时比较,THP-1巨噬细胞CD36表达增加最明显(P＜0.05),差异有统计学意义.其他组问比较差异无统计学意义.结论.THP-1巨噬细胞与不同浓度Hcy(0、0.01、0.05、0.1、0.2 mmol/L)孵育24 h后,Hcy可使THP-1巨噬细胞CD36的表达增加,且呈剂量依赖关系;与0.1 mmol/L Hcy培养不同时间(0、3、6、12、24、48 h),也可使THP-1巨噬细胞CD36的表达增加,并呈时间依赖关系.高浓度Hcy可以上调巨噬细胞CD36分子的表达.     

同型半胱氨酸诱导人单核细胞分泌趋化因子的氧化应激机制的实验研究

目的探讨同型半胱氨酸（Hcy）诱导人单核细胞分泌趋化因子的致炎症作用及其氧化应激的机制,明确大剂量叶酸在这一过程中的潜在作用。方法用Hcy（100μmol／L）和叶酸（5μmol／L）处理人单核细胞24h。使用酶联免疫吸附实验检测单核细胞趋化蛋白-1（MCP-1）、IL-8水平（n=8）。应用激光共聚焦显微镜探测单核细胞内氧自由基（ROS）的表达。使用细胞色素C还原法评价单核细胞内NADPH氧化酶活性。结果Hey显著增加了单核细胞对趋化因子MCP-1的分泌[对照组（1．88±0．51）ng／ml比Hey处理组（4．36±0．72）ng／ml,P〈0．05],而叶酸显著抑制了Hcy诱导的单核细胞分泌MCP-1[Hey处理组（4．36±0．72）ng／ml比Hey与叶酸共同处理组（2．40±0．60）ng／ml,P〈0．05]。此外,Hey显著增加了单核细胞对趋化因子IL-8的分泌[对照组（4．9±1．9）ng／ml比Hey处理组（12．7±1．5）,P〈0．05],而叶酸明显抑制了这一过程[Hey处理组（12．7±1．5）比Hey与叶酸共同处理组（7．2±1．9）ng／ml,P〈0．05]。Hcy（100μmol/L）显著增加了单核细胞ROS产生[对照组100％比Hey处理组（443．0±60．9）％,P〈0．05],叶酸（5μmol／L）抑制了Hcy诱导的单核细胞ROS产生[Hey处理组（443．0±60．9）％比Hey与叶酸共同处理组（133．0±34．7）％,P〈0．05]。Hey显著增加了单核细胞NADPH氧化酶的活力[对照组100％比Hey处理组（520±80）％,P〈0．05],叶酸（5μmol／L）及NADPH氧化酶的抑制剂DPI明显降低了Hcy诱导的人单核细胞NADPH氧化酶的活性[Hcy处理组（520±80）％比Hcy与叶酸共同处理组（310±70）％比Hcy与DPI共同处理组（280±40）％,P〈0．05]。结论Hcy可能通过活化NADPH氧化酶的途径,诱导ROS的产生及分泌趋化因子,叶酸可能通过降低NADPH氧化酶活性这一途径抑制Hcy诱导的ROS的产生及趋化因子的分泌。提示Hcy可能通过诱导炎症的机制促进动脉粥样硬化的发展,叶酸可能通过降低Hcy水平以外的抗氧化机制,对动脉粥样硬化发挥潜在的有益作用。     

同型半胱氨酸对巨噬细胞CD147表达的影响及瑞舒伐他汀的干预作用

目的探讨同型半胱氨酸对U-937巨噬细胞CD147表达的影响及瑞舒伐他汀的干预作用。方法在佛波酯诱导分化的人U-937巨噬细胞中加入0、50、100及500μmol/L的同型半胱氨酸孵育48 h;半定量RT-PCR检测CD147 mRNA的表达,Western blot检测巨噬细胞CD147蛋白的表达。不同浓度的瑞舒伐他汀和500μmol/L同型半胱氨酸共同干预U-937巨噬细胞,48 h后半定量RT-PCR及Western blot检测CD147受抑制情况,细胞免疫荧光试验检测CD147表达。结果半定量RT-PCR和Western blot结果显示,随同型半胱氨酸浓度增加,U-937巨噬细胞CD147 mRNA及蛋白的表达逐渐升高,具有剂量依赖性。不同浓度瑞舒伐他汀和500μmol/L同型半胱氨酸共同处理U-937巨噬细胞,随瑞舒伐他汀浓度增加,U-937巨噬细胞CD147 mRNA及蛋白的表达逐渐受抑制,呈一定剂量依赖性。细胞免疫荧光证实同型半胱氨酸促进CD147表达增加,而瑞舒伐他汀能抑制其表达。结论同型半胱氨酸能上调U-937巨噬细胞CD147的表达,瑞舒伐他汀呈浓度依赖性抑制同型半胱氨酸诱导CD147表达。     

同型半胱氨酸在缺血性脑血管病发病中的作用

脑血管病是严重危害人类健康的常见、多发病,其特征是病死率、致残率和复发率高;目前,WHO已将其列为需迫切解决的公共卫生问题之一。缺血性脑血管病（ICVD）作为脑血管病的重要亚型,其发病机制尚未完全阐明。研究显示,同型半胱氨酸（Hcy）与心脑血管疾病发生密切相关,高     

同型半胱氨酸与动脉粥样硬化性血管病

血浆高同型半胱氨酸血症作为导致动脉粥样硬化性血管病的独立的危险因素正日益受到人们的关注。本文从同型半胱氨酸的来源、代谢和影响因素、高同型半胱氨酸血症与动脉粥样硬化性血管病的关系及其防治作一初步概述。     

同型半胱氨酸调控miRNA在心血管疾病中的作用研究进展

同型半胱氨酸(Hcy)是由蛋氨酸代谢生成的中间代谢产物,大量研究发现Hcy与心血管疾病有很大关系。微小RNA(miRNA)是一大类短链非编码RNA,已在多种疾病中证实miRNA失调可导致疾病的发生发展,比如免疫紊乱、糖尿病、癫痫、癌症等。目前miRNA因其在心血管系统中的关键作用而被认为是心血管疾病的新治疗策略。当前研究已证实Hcy与miRNA均是心血管疾病的危险因素,Hcy可通过调控miRNA影响心血管疾病,miRNA也可能对Hcy引起相应变化。但Hcy与miRNA的相互影响在心血管疾病中的作用还有待明确。本文简要综述了Hcy调控miRNA在心血管疾病中的作用进展及其潜在的临床应用价值。     

Serum uric acid correlates with extracellular superoxide dismutase activity in patients with chronic heart failure

Increased serum uric acid has been identified as an independent risk factor for cardiovascular disease. However, because of its antioxidant capacity, uric acid may play a beneficial role in endothelial function. This paradoxical relationship between uric acid and endothelial function in chronic heart failure patients remains poorly understood. Thirty-eight chronic heart failure patients (New York Heart Association functional class II-III, mean age 58+/-10 years and mean left ventricular ejection fraction 25+/-8%) and twelve age-and-sex-matched healthy controls were studied. Chronic heart failure patients showed higher uric acid levels (7.3+/-2.3 mg/dL vs. 6.1+/-0.2 mg/dL, p<0.05) and lower extracellular superoxide dismutase activity (136+/-36 U ml(-1) min(-1) vs. 203+/-61 U ml(-1) min(-1), p<0.01) and endothelium-dependent vasodilatation (4.0+/-1.6% v. 9.1+/-3.0%, p<0.01) when compared with control subjects. In chronic heart failure patients, correlations between both uric acid levels and extracellular superoxide dismutase activity (r=0.45; p<0.01), and uric acid and endothelium-dependent vasodilatation (r=0.35; p=0.03) were detected. These correlations were not observed in healthy individuals, suggesting a positive effect of uric acid on endothelial function partially mediated by modulation of extracellular superoxide dismutase activity in chronic heart failure.     

高同型半胱氨酸血症中的氧化损伤机制的临床研究

目的 :评价高同型半胱氨酸 (Hcy)血症中的氧化损伤机制。方法 :所有入选者均接受冠状动脉造影明确有无冠心病 ,并通过高压液相色谱仪测量血浆Hcy浓度。以高于 15 μmol/L为标准 ,分为高Hcy血症组〔(病例组 ) 4 9例〕与对照组 (70例 )。所有入选者均测量血浆超氧化物歧化酶 (SOD)和丙二醛 (MDA)浓度。结果 :高Hcy血症组的血浆MDA水平升高 ,与对照组比较差异有显著性意义 (P <0 .0 5 ) ,高Hcy血症组血浆SOD水平较对照组增高 ,但差异无显著性意义 (P >0 .0 5 )。结论 :氧化损伤是Hcy的毒性作用机制之一     

白藜芦醇对去卵巢骨质疏松大鼠血同型半胱氨酸和氧化应激指标的影响

目的 观察白藜芦醇对去卵巢骨质疏松大鼠血同型半胱氨酸(Hcy)和氧化应激指标的影响.方法 32只3月龄雌性Sprague-Dawley (SD)大鼠,按随机数字表法分为4组:去卵巢组、乙烯雌酚组、白藜芦醇组和假手术组,每组8只.去卵巢组、乙烯雌酚组和白藜芦醇组大鼠行双侧卵巢切除术复制骨质疏松模型.术后1周开始灌胃给药,假手术组和去卵巢组大鼠给予蒸馏水(每日一次),其余两组大鼠分别予乙烯雌酚0.03 mg·kg-1·d-1和白藜芦醇20 mg·kg-1·d-1.治疗10周后,测定大鼠血浆总Hcy (tHcy)、总抗氧化能力(TAC)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛水平,取L5椎体和右股骨进行骨密度测定.结果 与假手术组相比,去卵巢组血浆tHcy和丙二醛水平升高,TAC和GSH-Px水平下降;与去卵巢组相比,乙烯雌酚组和白藜芦醇组血浆tHcy和丙二醛浓度均明显降低,TAC和GSH-Px水平显著升高(F=19.709,117.219,7.020,20.544,P均＜0.01);白藜芦醇组血浆丙二醛浓度较乙烯雌酚组升高(F=117.219,P＜0.01).与假手术组相比,去卵巢组腰椎和股骨骨密度均明显降低;与去卵巢组相比,乙烯雌酚组腰椎和股骨骨密度明显升高,接近假手术组水平(P＞0.05);白藜芦醇组腰椎和股骨骨密度升高,但仍低于乙烯雌酚组和假手术组(F=48.518,43.263,P均＜0.01).血浆tHcy与腰椎和股骨骨密度呈负相关(r=-0.663,P＜0.001;r=-0.520,P =0.002),TAC与股骨骨密度呈正相关(r=0.539,P=0.001).结论 高Hcy血症和氧化应激与去卵巢大鼠骨质疏松关系密切.白藜芦醇可能通过降低血浆tHcy水平和改善氧化应激,对去卵巢大鼠骨质疏松发挥保护作用.     

锰超氧化物歧化酶抑癌作用的研究进展

锰超氧化物歧化酶(manganese superoxide dismutase,MnSOD)是真核细胞内重要的抗氧化酶.它是潜在的新型肿瘤抑制基因,具有抑制肿瘤细胞生长的功能,在肿瘤中表达异常.此文综述了MnSOD抑癌作用及其作为肿瘤基因治疗新靶位的研究进展.     

Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischaemic heart disease: a double-blind, randomized controlled study.

AIMS: This randomized controlled study was designed to determine whether oral coenzyme Q(10) (CoQ(10)) supplementation (100 mg tid) was able to improve extracellular superoxide dismutase (ecSOD) activity and endothelium-dependent (ED) vasodilation in patients with coronary artery disease (CAD). ecSOD, a major antioxidant enzyme system of the vessel wall, is reduced in patients with CAD. Moreover, there is a strong correlation between endothelium-bound ecSOD and the ED dilation of conduit arteries. CoQ(10) has been recently shown to improve the ED relaxation in diabetic patients. METHODS AND RESULTS: Thirty-eight CAD patients (33 M/5 F, mean age 55 +/- 4 years, ejection fraction 57.5 +/- 8%) were randomized into two groups. One group (n = 19) received CoQ(10) orally at doses of 300 mg/day for 1 month, whereas the other group received a placebo. On entry and after 1 month, all patients underwent brachial artery ED assessment, cardiopulmonary exercise test, and the measurement of endothelium-bound ecSOD activity. A total of 33 patients completed the study. ecSOD, ED relaxation, as well as peak VO(2) and O(2) pulse increases in the CoQ(10)-treated group were statistically greater vs. the variations in the placebo group. In particular, improvements elicited by CoQ(10) supplementation were remarkable in subjects presenting low initial endothelium-bound ecSOD and thus more prone to oxidative stress. CONCLUSION: Improvements in the ED relaxation and endothelium-bound ecSOD activity might be related to CoQ(10) capability of enhancing endothelial functionality by counteracting nitric oxide oxidation. The enhancement of peak VO(2) and of O(2) pulse is likely due to the bioenergetic effect of CoQ(10); on the other end, the improved VO(2) could also depend on the observed enhanced peripheral endothelial function.     

Serum manganese superoxide dismutase and thioredoxin are potential prognostic markers for hepatitis C virus-related hepatocellular carcinoma

AIM:To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus(HCV)related hepatocellular carcinoma(HCC).METHODS:Sixty-four consecutive patients who were admitted to Kagoshima University Medical and Dental Hospital were enrolled in this retrospective study.All patients had chronic liver disease(CLD) due to infection with HCV.Thirty patients with HCV-related HCC,34 with HCV-related CLD without HCC(non-HCC),and 20 healthy volunteers(HVs) were enrolled.Possible associa...     

Evidence of oxidative stress in chronic heart failure in humans

Chronic heart failure (CHF) due to coronary artery disease (CAD)has been shown to be associated with increased plasma thiobarbituricreactive substances (TBARS) and reduced plasma thiol (PSH) concentrations,suggesting oxidative stress (OS). The aims of the present studieswere (a) to determine whether OS is due to CAD or CHF per seand (b) to determine if a wider range of more specific markersof OS are abnormal in CHF. In the first study, two groups of patients (n = 15 each) werecompared. Group 1 (11 male, mean age 56 years) had CHF due toCAD and group 2 (12 male, mean age 53 years) had non-CAD CHF.Median plasma TBARS in controls was 7.6 nmol . ml^–1 ,10.0 nmol . m^–1 in group 1 and 9.3 nmol. ml^–1 ingroup 2 (P < 0.01 both groups vs control). Median PSH was505 384 and 364 nmol. ml^–1 (P < 0.05 and P < 0.01vs control) respectively. Fifty-three patients with CHF were recruited in the second study.Malondialdehyde and PSH were 10.3 and 409 nmol. ml^–1 respectively,compared to control values of 7.9 and 560 nmol. ml^.1 (both P< 0.001). The median values for the following additionalmeasures of OS in controls and patients were: erythrocyte superoxidedismustase 131 vs 114 U . l^–1 (P = 0.005); caeruloplasminoxidase 97 vs 197 U. l^–1 (P < 0.01); erythrocyte glutathione1.56 nmol . ml^–1 vs 1.77 nmol . ml^–1 (P < 0.02);plasma conjugated dienes 0.28 vs 0.33 optical density units(P = ns). Chronic heart failure, regardless of aetiology, is associatedwith abnormalities of a range of markers of OS.