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在终末期肾病中,通过磁共振波谱和近红外光谱法研究补充肉碱对肌肉代谢的影响。

Effects of carnitine supplementation on muscle metabolism by the use of magnetic resonance spectroscopy and near-infrared spectroscopy in end-stage renal disease.

作者信息

Vaux E C, Taylor D J, Altmann P, Rajagopalan B, Graham K, Cooper R, Bonomo Y, Styles P

机构信息

Oxford Kidney Unit, Churchill Hospital, Headington, UK.

出版信息

Nephron Clin Pract. 2004;97(2):c41-8. doi: 10.1159/000078399.

DOI:10.1159/000078399
PMID:15218329
Abstract

BACKGROUND/AIM: A defect in skeletal muscle mitochondrial metabolism develops in patients with chronic renal failure on haemodialysis. Treatment with carnitine, a compound essential for normal mitochondrial function, has been suggested to have significant benefits in such patients, so we carried out a study to see if carnitine acts by improving muscle bioenergetics and function.

METHODS

In a phase II randomised double-blind trial, patients with end-stage renal disease received placebo or intravenous L-carnitine (20 mg/kg dry body weight three times weekly after haemodialysis) for 16 weeks (n = 13 in each group). 31P magnetic resonance spectroscopy, 1H magnetic resonance imaging and near-infrared spectroscopy were used to measure muscle bioenergetics and function at baseline and at 16 weeks.

RESULTS

There were no significant differences between groups at baseline. Mean plasma carnitine rose 10-fold in the carnitine group but was unchanged in the placebo group. L-carnitine had no statistically significant effect on any of the parameters measured. The rate of proton efflux from muscle, as a measure of tissue perfusion, was low in both groups and was not affected by treatment.

CONCLUSIONS

The study failed to show any significant effect of 16 weeks' L-carnitine supplementation on these objective measures of muscle metabolism and function. Slow proton efflux from muscle provides evidence supporting low blood flow and, therefore, decreased oxygen availability, as an underlying mechanism for muscle mitochondrial dysfunction in this disorder.

摘要

背景/目的:接受血液透析的慢性肾衰竭患者会出现骨骼肌线粒体代谢缺陷。肉碱是正常线粒体功能所必需的一种化合物,有研究表明用其治疗这类患者会有显著益处,因此我们开展了一项研究,以观察肉碱是否通过改善肌肉生物能量学和功能发挥作用。

方法

在一项II期随机双盲试验中,终末期肾病患者接受安慰剂或静脉注射L-肉碱(血液透析后每周三次,每次20mg/kg干体重)治疗16周(每组n = 13)。在基线和16周时,使用31P磁共振波谱、1H磁共振成像和近红外光谱来测量肌肉生物能量学和功能。

结果

两组在基线时无显著差异。肉碱组的平均血浆肉碱升高了10倍,而安慰剂组则无变化。L-肉碱对所测量的任何参数均无统计学显著影响。作为组织灌注指标的肌肉质子外流率在两组中均较低,且不受治疗影响。

结论

该研究未能显示补充16周L-肉碱对这些肌肉代谢和功能的客观指标有任何显著影响。肌肉质子外流缓慢提供了证据,支持低血流量以及因此导致的氧供应减少是该疾病中肌肉线粒体功能障碍的潜在机制。

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