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

本研究的目的是阐明自由基相关产物在神经肌肉疾病中的表达及其机制。高血糖加剧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、再灌注24小时后，糖尿病大鼠坐骨神经中过氧化脂质和松散髓磷脂浓度显著升高，非糖尿病大鼠坐骨神经中无过氧化脂质浓度升高。由于缺血再灌注产生的氧自由基的影响，松弛髓磷脂可能会增加，而高血糖会加剧这种影响。线粒体里的红色纤维！免疫组化对脑肌病、Mn-SOD、ec-NOS、硝基酪氨酸进行强染色。然后在破红纤维上进行Fas、Fas配体、caspase 3、caspase 9、Bax、Apaf-1、bcl-2免疫染色。因此，自由基损伤可能导致线粒体脑肌病的红纤维发生凋亡。在包涵体肌炎和边缘空泡型远端肌病中，Fas在带空泡的纤维中高表达。这些疾病的发病机制可能与Fas相关的细胞凋亡有关。然而，在多发性肌炎中，Fas不表达。另一方面，在皮肌炎中，tenacin在组织间质区呈网状染色。Tenacin也显示筋环周围萎缩。Tenacin是诊断皮肌炎非常有用的指标。观察心肌毒素致心肌坏死大鼠再生骨液中肌营养不良蛋白、α-肌聚糖、β-肌营养不良聚糖、α- syntrophin和nNOS的表达。再生从基底膜侧向肌下侧推进，从基底膜结构相关蛋白向信号传递相关蛋白推进。nNOS的表达与肌纤维类型分化有关，nNOS的作用与肌肉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.