肌肉中7α-和7β-氢过氧化胆甾-5-烯-3β-醇作为氧化应激指标：对大鼠乙醇剂量的反应

7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol in muscle as indices of oxidative stress: response to ethanol dosage in rats.

作者信息

Adachi J, Asano M, Ueno Y, Reilly M, Mantle D, Peters T J, Preedy V R

机构信息

Department of Legal Medicine, Kobe University School of Medicine, Japan.

出版信息

Alcohol Clin Exp Res. 2000 May;24(5):675-81.

PMID:10832909

Abstract

BACKGROUND

Alcohol-induced muscle disease (AIMD) encompasses both acute and chronic lesions, and affected patients exhibit concomitant functional and structural lesions. The pathogenic mechanisms are unknown, although it is possible that defects in the membrane-lipid domain are involved. Therefore, the effect of acute ethanol on membrane lipid from rat skeletal muscles (control, n = 7; ethanol, n = 7) was investigated.

METHODS

Soleus and plantaris skeletal muscles were collected 24 hr after a single dose of 75 mmol/kg of ethanol. Lipids were analyzed by high-performance liquid chromatography with postcolumn chemiluminescence.

RESULTS

We found that two cholesterol-derived hydroperoxides, 7alpha-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH) and 7beta-hydroperoxycholest-5-en-3beta-ol (7beta-OOH) were present in soleus muscles of control animals (1.29 nmol/g and 3.20 nmol/g, respectively) and in plantaris (1.83 and 5.18 nmol/g, respectively). These hydroperoxides were significantly elevated by acute ethanol, in not only plantaris but also soleus skeletal muscle of rats. In contrast, protein carbonyl concentration, another indicator of oxidative stress, albeit to proteins, was not significantly affected in either soleus or plantaris muscles of ethanol dosed rats. In addition, gas chromatographic study of fatty acid composition from phospholipid of rat muscle showed a significant increase of 18:2 by ethanol in plantaris as well as soleus. Concomitant decreases occurred in the nonessential/essential fatty acid ratios.

CONCLUSIONS

This is the first report on 7alpha-OOH and 7beta-OOH accumulation in rat skeletal muscle, and it seems to reflect greater oxidative stress in the pathology of muscle of rats treated with acute ethanol. Together with the elevation of 18:2, these results signify perturbations in membrane lipids in response to ethanol, which may have important implications for the pathogenesis of alcohol-induced muscle disorders.

摘要

背景

酒精性肌病（AIMD）包括急性和慢性病变，受影响的患者同时存在功能和结构损伤。尽管膜脂区域缺陷可能参与其中，但其致病机制尚不清楚。因此，研究了急性乙醇对大鼠骨骼肌膜脂的影响（对照组，n = 7；乙醇组，n = 7）。

方法

单次给予75 mmol/kg乙醇24小时后，采集比目鱼肌和跖肌。脂质通过柱后化学发光的高效液相色谱法进行分析。

结果

我们发现，两种胆固醇衍生的氢过氧化物，7α-氢过氧胆甾-5-烯-3β-醇（7α-OOH）和7β-氢过氧胆甾-5-烯-3β-醇（7β-OOH）存在于对照动物的比目鱼肌中（分别为1.29 nmol/g和3.20 nmol/g）以及跖肌中（分别为1.83和5.18 nmol/g）。急性乙醇不仅使大鼠的跖肌，也使比目鱼肌中的这些氢过氧化物显著升高。相比之下，氧化应激的另一个指标——蛋白质羰基浓度，尽管是针对蛋白质的，但在给予乙醇的大鼠的比目鱼肌或跖肌中均未受到显著影响。此外，对大鼠肌肉磷脂脂肪酸组成的气相色谱研究表明，乙醇使跖肌和比目鱼肌中的18:2显著增加。非必需/必需脂肪酸比值随之降低。