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终末期肾病长期血液透析患者的血清对氧磷酶活性、高敏 C 反应蛋白和脂蛋白紊乱。

Serum paraoxonase activity, high-sensitivity C-reactive protein, and lipoprotein disturbances in end-stage renal disease patients on long-term hemodialysis.

机构信息

Laboratory of Research on Lipoproteins and Atherosclerosis, Faculty of Sciences Ben M'sik, B.P. 7955, Sidi Othman, Casablanca, Morocco; Laboratory of Biochemistry, Pasteur Institute of Morocco, Casablanca, Morocco.

出版信息

J Clin Lipidol. 2008 Feb;2(1):43-50. doi: 10.1016/j.jacl.2007.12.003. Epub 2008 Jan 4.

Abstract

BACKGROUND

Hemodialysis patients are at high risk for atherosclerotic events. Enhanced oxidant stress, dyslipidemia, and inflammation may have a major role in this risk. In this work, we assessed lipoprotein status, total homocysteine, high-sensitivity C-reactive protein (hs-CRP), and paraoxonase activity in hemodialysis patients to determine the correlations among these parameters and to compare these values with those measured in normal control subjects.

METHODS

We enrolled 109 end-stage renal disease patients on long-term hemodialysis and 100 age- and gender-matched healthy subjects. Total cholesterol, triglycerides, and high-density lipoprotein cholesterol levels were evaluated using colorimetric methods. Low-density lipoprotein (LDL) cholesterol was calculated according to the Friedewald formula. Serum levels of hs-CRP, apolipoproteins (Apo) AI, B, E, and lipoprotein(a) were measured by nephelometry. Lipoprotein particle (Lp) A-I and LpA-I:A-II were determined by immunoelectrophoresis. Total homocysteine levels were evaluated by the fluorescence polarization immunoassay method. Paraoxonase activity was determined using the paraoxon-like substrate.

RESULTS

Compared with controls, hemodialysis patients had more frequent atherogenic dyslipidemia, hyperhomocysteinemia, and elevated hs-CRP levels. These latter findings inversely correlate with ApoA-I and LpA-I:A-II and positively with ApoB, lipoprotein(a), and ApoB/ApoA-I ratio. Homocysteine levels correlated positively with age. Paraoxonase activity was decreased in hemodialysis patients, especially in elderly patients. This enzyme activity positively correlated with LpA-I:A-II, and inversely with hs-CRP, LDL-cholesterol, and ApoE levels.

CONCLUSION

The present study demonstrated an abnormal lipoprotein profile associated with increased hs-CRP and decreased paraoxonase activity in hemodialysis patients. Hence, inflammation, dyslipidemia, and increased oxidant stress linked to uremia may be contributors to increased cardiovascular risk in this population.

摘要

背景

血液透析患者发生动脉粥样硬化事件的风险较高。增强的氧化应激、血脂异常和炎症可能在这种风险中起主要作用。在这项工作中,我们评估了血液透析患者的脂蛋白状态、总同型半胱氨酸、高敏 C 反应蛋白(hs-CRP)和对氧磷酶活性,以确定这些参数之间的相关性,并将这些值与正常对照组进行比较。

方法

我们招募了 109 名长期血液透析的终末期肾病患者和 100 名年龄和性别匹配的健康对照者。使用比色法评估总胆固醇、甘油三酯和高密度脂蛋白胆固醇水平。根据 Friedewald 公式计算低密度脂蛋白(LDL)胆固醇。通过散射比浊法测量血清 hs-CRP、载脂蛋白(Apo)AI、B、E 和脂蛋白(a)水平。通过免疫电泳法测定脂蛋白颗粒(Lp)A-I 和 LpA-I:A-II。通过荧光偏振免疫测定法评估总同型半胱氨酸水平。使用对氧磷类似底物测定对氧磷酶活性。

结果

与对照组相比,血液透析患者更频繁地发生致动脉粥样硬化血脂异常、高同型半胱氨酸血症和 hs-CRP 水平升高。这些发现与 ApoA-I 和 LpA-I:A-II 呈负相关,与 ApoB、脂蛋白(a)和 ApoB/ApoA-I 比值呈正相关。同型半胱氨酸水平与年龄呈正相关。血液透析患者的对氧磷酶活性降低,尤其是老年患者。这种酶活性与 LpA-I:A-II 呈正相关,与 hs-CRP、LDL 胆固醇和 ApoE 水平呈负相关。

结论

本研究表明,血液透析患者存在异常的脂蛋白谱,伴有 hs-CRP 升高和对氧磷酶活性降低。因此,与尿毒症相关的炎症、血脂异常和氧化应激增加可能是导致该人群心血管风险增加的原因。

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