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硬皮病患者血浆中的致断裂活性:氧化应激的生物标志物。

Clastogenic activity in the plasma of scleroderma patients: a biomarker of oxidative stress.

作者信息

Emerit I, Filipe P, Meunier P, Auclair C, Freitas J, Deroussent A, Gouyette A, Fernandes A

机构信息

Institut Biomédical des Cordeliers, Université Paris VI, et CNRS, France.

出版信息

Dermatology. 1997;194(2):140-6. doi: 10.1159/000246083.

DOI:10.1159/000246083
PMID:9094462
Abstract

BACKGROUND

Scleroderma patients exhibit increased chromosomal instability due to circulating clastogenic plasma factors (CF). Formation and action mechanisms of CF are mediated by superoxide. In addition, previous work detected inosine triphosphate (ITP) in the plasma of 2 patients, and the enzyme adenosine deaminase (ADA) was found to be increased.

OBJECTIVE

To study correlations between CF, ITP and ADA levels, CF and disease activity, as well as other biomarkers of oxidative stress.

METHODS

Clastogenic activity was evaluated by means of cytogenetic methods in 48 patients and 55 healthy subjects. ITP was detected by mass spectrometry and electrospray ionisation. ADA was measured with a colorimetric assay and malondialdehyde using the Yagi method.

RESULTS

Clastogenic activity was significantly increased in patients' plasma compared to controls. In 10 patients CF, ITP and ADA were studied simultaneously. All three parameters were increased in the 7 patients of subgroups 2 (skin and esophagus involvement) and 3 (skin plus multiple organ involvement). ITP was not detected in 2 patients of subgroup 1 (skin involvement only) with low ADA and CF values.

CONCLUSION

ITP, the deamination product of ATP, is one of the clastogenic and superoxide generating components of CF. The formation of this deamination product of ATP is probably related to the increase in ADA. CF are biomarkers of oxidative stress and can be used for evaluation of antioxidant treatments in scleroderma.

摘要

背景

硬皮病患者由于循环中的致染色体断裂血浆因子(CF)而表现出染色体不稳定性增加。CF的形成和作用机制由超氧化物介导。此外,先前的研究在2例患者的血浆中检测到三磷酸肌苷(ITP),并且发现腺苷脱氨酶(ADA)升高。

目的

研究CF、ITP和ADA水平之间的相关性,CF与疾病活动度之间的相关性,以及氧化应激的其他生物标志物。

方法

采用细胞遗传学方法对48例患者和55名健康受试者的致染色体断裂活性进行评估。通过质谱和电喷雾电离检测ITP。采用比色法测定ADA,采用矢木法测定丙二醛。

结果

与对照组相比,患者血浆中的致染色体断裂活性显著增加。对10例患者同时研究了CF、ITP和ADA。在2组(皮肤和食管受累)和3组(皮肤加多个器官受累)的7例患者中,所有三个参数均升高。在1组(仅皮肤受累)的2例ADA和CF值较低的患者中未检测到ITP。

结论

ITP是ATP的脱氨基产物,是CF的致染色体断裂和产生超氧化物的成分之一。ATP这种脱氨基产物的形成可能与ADA升高有关。CF是氧化应激的生物标志物,可用于评估硬皮病的抗氧化治疗。

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