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尿毒症、糖尿病和动脉粥样硬化与抗氧化机制受损有关吗?

Are uremia, diabetes, and atherosclerosis linked with impaired antioxidant mechanisms?

作者信息

Dursun Belda, Dursun Evrim, Capraz Irfan, Ozben Tomris, Apaydin Ali, Suleymanlar Gultekin

机构信息

Department of Medicine, Pamukkale University Medical School, Denizli, Turkey.

出版信息

J Investig Med. 2008 Feb;56(2):545-52. doi: 10.2310/JIM.0b013e3181641ce3.

DOI:10.2310/JIM.0b013e3181641ce3
PMID:18317439
Abstract

BACKGROUND

Oxidative stress is a new risk factor for atherosclerosis. Increased oxidative stress in hemodialysis (HD) patients may arise from uremia-associated metabolic/humoral abnormalities and bioincompatibility of dialysis. Patients with diabetes mellitus (DM) may be subject to an additional risk. Respective influences of uremia, diabetes, and HD duration in accelerated atherosclerosis and oxidative stress have not been clarified yet.

METHODS

The study was performed on 24 nondiabetic HD patients, 23 diabetic HD patients, 20 stages 3 to 4 chronic kidney disease patients, and 21 diabetic patients without overt nephropathy. Carotid intima-media thickness, a surrogate of atherosclerosis, was measured by high-resolution B-mode ultrasonography. Oxidant status was determined by lipid peroxidation as expressed by malondialdehyde (MDA); antioxidant status was determined by superoxide dismutase, catalase, glutathione peroxidase, reduced intracellular glutathione, and plasma thiol.

RESULTS

Intima-media thickness (IMT) was higher in patients undergoing HD but not different between nondiabetic HD patients and diabetic HD patients. No correlation was found between the duration of HD and intima-media thickness. Antioxidants were generally lower in HD patients. Intima-media thickness was positively correlated with MDA and negatively correlated with plasma thiol. Among other risk factors, only age was correlated with intima-media thickness.

CONCLUSIONS

Increased carotid IMT in HD patients is independent of duration of HD or diabetes status. Age and MDA are the significant predictors of carotid IMT. Increased oxidative stress due to impaired antioxidant mechanisms, particularly reduced plasma thiol redox potential, may account for accelerated atherosclerosis in high-risk patients with chronic kidney failure and/or DM.

摘要

背景

氧化应激是动脉粥样硬化的一个新的危险因素。血液透析(HD)患者氧化应激增加可能源于尿毒症相关的代谢/体液异常以及透析的生物不相容性。糖尿病(DM)患者可能面临额外的风险。尿毒症、糖尿病和HD持续时间对加速动脉粥样硬化和氧化应激的各自影响尚未阐明。

方法

对24例非糖尿病HD患者、23例糖尿病HD患者、20例3至4期慢性肾脏病患者和21例无明显肾病的糖尿病患者进行了研究。通过高分辨率B型超声测量颈动脉内膜中层厚度,作为动脉粥样硬化的替代指标。通过丙二醛(MDA)表达的脂质过氧化来确定氧化状态;通过超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、细胞内还原型谷胱甘肽和血浆硫醇来确定抗氧化状态。

结果

HD患者的内膜中层厚度(IMT)较高,但非糖尿病HD患者和糖尿病HD患者之间无差异。未发现HD持续时间与内膜中层厚度之间存在相关性。HD患者的抗氧化剂水平普遍较低。内膜中层厚度与MDA呈正相关,与血浆硫醇呈负相关。在其他危险因素中,只有年龄与内膜中层厚度相关。

结论

HD患者颈动脉IMT增加与HD持续时间或糖尿病状态无关。年龄和MDA是颈动脉IMT的重要预测因素。抗氧化机制受损导致的氧化应激增加,特别是血浆硫醇氧化还原电位降低,可能是慢性肾衰竭和/或DM高危患者动脉粥样硬化加速的原因。

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