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自由基在高同型半胱氨酸血症中作为内皮细胞损伤介质的作用。

The role of free radicals as mediators of endothelial cell injury in hyperhomocysteinemia.

作者信息

Clarke R, Naughten E, Cahalane S, Sullivan K O, Mathias P, McCall T, Graham I

机构信息

Department of Cardiology, Adelaide Hospital, Dublin.

出版信息

Ir J Med Sci. 1992 Sep;161(9):561-4. doi: 10.1007/BF02940559.

DOI:10.1007/BF02940559
PMID:1428778
Abstract

Hyperhomocysteinemia has been suggested as a potent new risk factor for premature cardiovascular disease. Homocsyteine can induce endothelial cell injury but the mechanism is not understood. The purpose of this study was to evaluate the role of free radicals as potential causes of endothelial cell injury in a case-control study of obligate heterozygotes for cystathionine beta-synthase deficiency. Firstly, free radical production as measured by neutrophil chemiluminescence in obligate heterozygotes for cystathionine beta-synthase deficiency was compared with age- and sex-matched normal subjects. Secondly, the response of the cellular antioxidant system was examined by measuring the enzymes superoxide dismutase and glutathione peroxidase, their cofactors (selenium, copper), vitamin E and vitamin A in heterozygotes and normal subjects. Analyses of neutrophil chemiluminescence, vitamin A and E, glutathione peroxidase, selenium and copper showed no difference between heterozygotes and controls. While superoxide dismutase activity was higher in heterozygotes than normal subjects, the difference did not reach statistical significance and the hypothesis of excess free radical production as a mechanism of injury was not confirmed. However, further examination of superoxide dismutase activity in a larger number of subjects would be of interest.

摘要

高同型半胱氨酸血症已被认为是早发性心血管疾病的一种新的重要危险因素。同型半胱氨酸可诱导内皮细胞损伤,但其机制尚不清楚。本研究的目的是在一项关于胱硫醚β-合酶缺乏症的 obligate 杂合子的病例对照研究中,评估自由基作为内皮细胞损伤潜在原因的作用。首先,将胱硫醚β-合酶缺乏症的 obligate 杂合子中通过中性粒细胞化学发光测定的自由基产生与年龄和性别匹配的正常受试者进行比较。其次,通过测量杂合子和正常受试者中的超氧化物歧化酶和谷胱甘肽过氧化物酶、它们的辅助因子(硒、铜)、维生素E和维生素A,来检查细胞抗氧化系统的反应。中性粒细胞化学发光、维生素A和E、谷胱甘肽过氧化物酶、硒和铜的分析显示杂合子与对照组之间没有差异。虽然杂合子中的超氧化物歧化酶活性高于正常受试者,但差异未达到统计学意义,作为损伤机制的自由基产生过多的假设未得到证实。然而,在更多受试者中进一步检查超氧化物歧化酶活性将是有意义的。

相似文献

1
The role of free radicals as mediators of endothelial cell injury in hyperhomocysteinemia.自由基在高同型半胱氨酸血症中作为内皮细胞损伤介质的作用。
Ir J Med Sci. 1992 Sep;161(9):561-4. doi: 10.1007/BF02940559.
2
Hyperhomocysteinemia: an independent risk factor for vascular disease.高同型半胱氨酸血症:血管疾病的独立危险因素。
N Engl J Med. 1991 Apr 25;324(17):1149-55. doi: 10.1056/NEJM199104253241701.
3
Increased plasma copper in patients with homocystinuria due to cystathionine beta-synthase deficiency.由于胱硫醚β-合酶缺乏导致的同型胱氨酸尿症患者血浆铜升高。
Clin Chim Acta. 1983 Jan 7;127(1):105-13. doi: 10.1016/0009-8981(83)90080-3.
4
Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine beta-synthase deficiency.维生素B12缺乏时血浆总同型半胱氨酸水平高于因胱硫醚β合酶缺乏导致的同型胱氨酸尿症杂合子状态时的水平。
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Cystathionine beta synthase deficiency induces catalase-mediated hydrogen peroxide detoxification in mice liver.胱硫醚β合酶缺乏诱导小鼠肝脏中过氧化氢酶介导的过氧化氢解毒。
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Cystathionine-beta-synthase deficiency: detection of heterozygotes by the ratios of homocysteine to cysteine and folate.胱硫醚-β-合酶缺乏症:通过同型半胱氨酸与半胱氨酸及叶酸的比率检测杂合子。
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Improved identification of heterozygotes for homocystinuria due to cystathionine synthase deficiency by the combination of methionine loading and enzyme determination in cultured fibroblasts.通过甲硫氨酸负荷试验与培养成纤维细胞中酶的测定相结合,改进对因胱硫醚合成酶缺乏所致同型胱氨酸尿症杂合子的识别。
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Genetic determinants of hyperhomocysteinaemia: the roles of cystathionine beta-synthase and 5,10-methylenetetrahydrofolate reductase.高同型半胱氨酸血症的遗传决定因素:胱硫醚β-合酶和5,10-亚甲基四氢叶酸还原酶的作用。
Eur J Pediatr. 2000 Dec;159 Suppl 3:S208-12. doi: 10.1007/pl00014405.
9
Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice.胱硫醚β-合酶缺陷小鼠的内皮功能障碍与S-腺苷同型半胱氨酸升高
Circ Res. 2001 Jun 8;88(11):1203-9. doi: 10.1161/hh1101.092180.
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[Homocysteine--a risk factor for atherosclerosis].[同型半胱氨酸——动脉粥样硬化的一个风险因素]
Orv Hetil. 2001 Jul 8;142(27):1439-44.

本文引用的文献

1
The disulfide of L-cysteine and L-homocysteine in urine of patients with cystinuria.胱氨酸尿症患者尿液中L-半胱氨酸和L-高半胱氨酸的二硫化物
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2
Homocysteine-induced endothelial cell injury in vitro: a model for the study of vascular injury.同型半胱氨酸诱导的体外内皮细胞损伤:一种用于研究血管损伤的模型。
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4
Moderate homocysteinemia--a possible risk factor for arteriosclerotic cerebrovascular disease.中度高同型半胱氨酸血症——动脉粥样硬化性脑血管疾病的一个潜在危险因素。
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5
The production of free radicals during the autoxidation of cysteine and their effect on isolated rat hepatocytes.半胱氨酸自氧化过程中自由基的产生及其对分离的大鼠肝细胞的影响。
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7
Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase.红细胞谷胱甘肽过氧化物酶的定量和定性特征研究。
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8
Homocystinemia. Vascular injury and arterial thrombosis.高胱氨酸血症。血管损伤与动脉血栓形成。
N Engl J Med. 1974 Sep 12;291(11):537-43. doi: 10.1056/NEJM197409122911101.
9
Generation of superoxide free radical during the autoxidation of thiols.硫醇自氧化过程中超氧自由基的产生。
J Biol Chem. 1974 Apr 10;249(7):2151-5.
10
Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease.同型胱氨酸尿症杂合子与外周和脑动脉过早闭塞性疾病
N Engl J Med. 1985 Sep 19;313(12):709-15. doi: 10.1056/NEJM198509193131201.