Studies of expression and mechanism of free-radical associated products in neuromuscular disorders.

本研究旨在阐明自由基相关产物在神经肌肉疾病中的表达及其机制。高血糖加重了大鼠周围神经缺血再灌注的影响。大鼠坐骨神经缺血2小时再灌流24小时后，糖尿病大鼠神经组织中脂质过氧化和松散髓鞘含量显著增加，而非糖尿病大鼠则无明显变化。由于缺血-再灌注产生的氧自由基的影响，松散的髓鞘可能会增加，而高血糖会加剧氧自由基的作用。脑肌病、Mn-SOD、EC-NOS、硝基酪氨酸免疫组织化学染色呈强阳性。Fas、Fas-Ligand、caspase3、caspase9、bax、APAF-1和bcl-2也被免疫组织化学染色。在包涵体肌炎和边框空泡型远端肌病中，Fas在有空泡的纤维中高表达。其发病机制可能与Fas相关的细胞凋亡有关。然而，在多发性肌炎中，Fas不表达。而在皮肌炎中，在间质区域，替那酸染色呈网状。泰纳金也表现出束周萎缩。肌萎缩侧索硬化症是一种非常有用的皮肌炎诊断标记物。本文观察了心脏毒素诱导的大鼠心肌坏死后再生骨骼粘液中肌营养不良蛋白、α-肌聚糖、β-肌营养不良蛋白、α-1-合营养素和一氧化氮合酶的表达。再生从基底膜侧向肌膜下侧推进，从与基底膜结构相关的蛋白向与信号传递相关的蛋白推进。NNOS的表达与肌纤维类型的分化有关，nNOS的作用与肌肉中2B型纤维的功能有关。

The aim of this study is to clarify the expression and mechanism of free-radical associated products in neuromuscular disorders.Hyperglycemia exacerbates the effect of ischemia-reperfusion on peripheral nerve in rat. After a 2-hour ischemia and 24-hour reperfusion of sciatic nerves of rats, the concentrations of lipid peroxide and loose myelin in the nerves were significantly increased in the diabetic rats, but not in the nondiabetic rats. Loose myelin may be increased as a result of the effects of oxygen free radicals produced by ischemia-reperfusion, which are exacerbated by hyperglycemia.On ragged -red fibers in mitochondria! Encephalomyopathies, Mn-SOD, ec-NOS, nitrotyrosine were strongly stained by immunohistochemistry. And then, Fas, Fas-ligand, caspase 3, caspase 9, Bax, Apaf-1 and bcl-2 were also immunostained on ragged-red fibers. Therefore, The free-radical injury may induce apoptosis in the ragged-red fibers of mitochondrial encephalomyopathies.In inclusion body myositis and rimmed-vacuole type distal myopathy, Fas was highly expressed in fibers with vacuole. The pathomechanism of the diseases may be involved of apoptosis associated with Fas. In polymyositis, however, Fas was not expressed. On the other hand, in dermatomyositis tenacin was stained in the network pattern in the interstitial areas. Tenacin also showed perifascicular atrophy. Tenacin is a very useful marker for diagnosis of dermatomyositis.The expression of dystrophin, α-sarcoglycan, β-dystropglycan, α1-syntrophin, and nNOS were evaluated in regeneration skeletal mucles of rats after cardiotoxin-induced myonecrosis. The regeneration advances from the basement menbrane side to the subsarcolemmal side and from the proteins associated with structure of the basement membrane to the proteins associated with signal transmitting. The expression of nNOS is related to the muscle fiber type differentiation, and the role of nNOS is related to the function of the type 2B fibers of the muscle.