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类风湿关节炎患者循环祖细胞:与炎症和氧化应激的关系。

Circulating progenitor cells in rheumatoid arthritis: association with inflammation and oxidative stress.

机构信息

Departments of Internal Medicine and Medical Therapy, University of Messina , Italy.

出版信息

Scand J Rheumatol. 2014;43(3):184-93. doi: 10.3109/03009742.2013.836564. Epub 2013 Dec 9.

Abstract

OBJECTIVES

To evaluate the association between inflammation, oxidative stress, and circulating progenitor cell (CPC) number and redox equilibrium, vascular lesions and accelerated atherosclerosis in rheumatoid arthritis (RA).

METHOD

Circulating CD34+ cells were isolated from 33 RA patients and 33 controls. Reactive oxygen species (ROS) levels and mRNA expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase type 1 (GPx-1) antioxidant enzymes, and the gp91phox-containing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase NOX2 were measured in CD34+ cells. C-reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR), carotid intima-media thickness (cIMT), and arterial stiffness (AS) were also evaluated. We investigated the relationships between inflammatory markers, vascular parameters, cell number, and antioxidant enzymes.

RESULTS

CD34+ cell number was lower in RA patients than in controls. In CD34+ cells from RA patients, ROS levels, MnSOD mRNA, and NOX2 mRNA were higher, while mRNA expression of GPx-1 and CAT was significantly lower. The AS, pulse wave velocity (PWV), and augmentation index (AIx) were higher, as was cIMT. CD34+ cell number was inversely correlated with CRP, ROS, PWV, and AIx, and with the CAT/MnSOD and GPx-1/MnSOD ratios. CRP was correlated with MnSOD mRNA, PWV, and AIx but not with CAT and GPx-1 mRNA.

CONCLUSIONS

Our data show a link between inflammation, oxidative stress, and the impairment of the antioxidant system of CPCs and their number, and with arterial stiffness in RA subjects. This could suggest a perspective on the accelerated development of vascular damage and atherosclerosis in RA.

摘要

目的

评估炎症、氧化应激与循环祖细胞(CPC)数量及氧化还原平衡、血管病变和类风湿关节炎(RA)加速动脉粥样硬化之间的关系。

方法

从 33 例 RA 患者和 33 例对照者中分离循环 CD34+细胞。测量 CD34+细胞中的活性氧(ROS)水平和锰超氧化物歧化酶(MnSOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶 1(GPx-1)抗氧化酶的 mRNA 表达,以及含有 gp91phox 的烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶 NOX2。还评估了 C 反应蛋白(CRP)、纤维蛋白原、红细胞沉降率(ESR)、颈动脉内膜-中层厚度(cIMT)和动脉僵硬度(AS)。我们研究了炎症标志物、血管参数、细胞数量和抗氧化酶之间的关系。

结果

RA 患者的 CD34+细胞数量低于对照组。在 RA 患者的 CD34+细胞中,ROS 水平、MnSOD mRNA 和 NOX2 mRNA 更高,而 GPx-1 和 CAT mRNA 的表达则显著降低。AS、脉搏波速度(PWV)和增强指数(AIx)更高,cIMT 也更高。CD34+细胞数量与 CRP、ROS、PWV 和 AIx 呈负相关,与 CAT/MnSOD 和 GPx-1/MnSOD 比值呈负相关。CRP 与 MnSOD mRNA、PWV 和 AIx 相关,但与 CAT 和 GPx-1 mRNA 不相关。

结论

我们的数据表明,炎症、氧化应激与 CPC 抗氧化系统及其数量的损伤之间存在联系,并且与 RA 患者的动脉僵硬度有关。这可能提示 RA 中血管损伤和动脉粥样硬化加速发展的一个观点。

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