Thomas P K, Cooper J M, King R H, Workman J M, Schapira A H, Goss-Sampson M A, Muller D P
Department of Neurological Science, Royal Free Hospital School of Medicine, London, UK.
J Anat. 1993 Dec;183 ( Pt 3)(Pt 3):451-61.
Vitamin E deficiency in rats gives rise to a neuromuscular syndrome that includes a peripheral neuropathy as well as generalised muscle wasting and weakness. This is probably related to damage by oxygen-derived free radicals. In the present study, histological examination of lower limb muscles showed widespread myopathic changes which included the presence of amorphous electron-dense inclusions and tubular aggregates in muscle fibres and muscle fibre necrosis. Histochemical observations suggested a reduction in the activity of oxidative enzymes. The mitochondria showed nonspecific degenerative changes on electron microscopy; no paracrystalline inclusions were observed. Polarographic analysis of isolated muscle mitochondria revealed statistically significant decreases in oxygen utilisation rates with both NADH and FADH2-linked substrates. In confirmation of a generalised respiratory chain abnormality, enzymatic analyses revealed decreases in the activities of complexes I, II/III and IV, although only the decreases in complexes I and IV activities were statistically significant. Measurements of membrane fluidity showed that this is reduced in mitochondria from vitamin E deficient rats, indicating reduced stability of their membranes. The respiratory control ratio, derived from the polarographic results, was also reduced in mitochondria from vitamin E deficient animals, suggesting membrane damage. An altered lipid environment, possibly secondary to a higher level of lipid peroxidation, could result in the inhibition of complexes I and IV. This could also be caused by oxidative damage to the complexes or to mitochondrial DNA. The preservation of citrate synthase activity is against any generalised defect of mitochondrial function. The question as to whether these defects of mitochondrial respiratory chain function are responsible for the muscle fibre damage and necrosis requires further investigation.
大鼠维生素E缺乏会引发一种神经肌肉综合征，包括周围神经病变以及全身性肌肉萎缩和无力。这可能与氧衍生自由基的损伤有关。在本研究中，对下肢肌肉的组织学检查显示广泛的肌病性改变，包括肌纤维中存在无定形电子致密包涵体和管状聚集物以及肌纤维坏死。组织化学观察表明氧化酶活性降低。线粒体在电子显微镜下显示非特异性退行性改变；未观察到副结晶包涵体。对分离的肌肉线粒体进行极谱分析发现，使用NADH和FADH2连接底物时氧利用率有统计学意义的降低。为证实存在全身性呼吸链异常，酶分析显示复合物I、II/III和IV的活性降低，尽管只有复合物I和IV活性的降低具有统计学意义。膜流动性测量表明，维生素E缺乏大鼠的线粒体膜流动性降低，表明其膜稳定性降低。根据极谱结果得出的呼吸控制率在维生素E缺乏动物的线粒体中也降低，提示膜损伤。脂质环境改变，可能继发于较高水平的脂质过氧化，可能导致复合物I和IV受到抑制。这也可能是由于复合物或线粒体DNA的氧化损伤所致。柠檬酸合酶活性的保留排除了线粒体功能存在任何全身性缺陷的可能性。线粒体呼吸链功能的这些缺陷是否是肌纤维损伤和坏死的原因，这一问题尚需进一步研究。
