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。高血压加重了缺血再灌注对大鼠周围神经的影响。大鼠坐骨神经缺血2 h再灌注24 h后，糖尿病大鼠神经内脂质过氧化物和松髓磷脂含量明显升高，而非糖尿病大鼠神经内脂质过氧化物和松髓磷脂含量无明显变化。由于缺血再灌注产生的氧自由基的影响，高血糖会加剧这种影响，从而导致疏松的髓鞘增加。脑肌病、Mn-SOD、ec-NOS、硝基酪氨酸免疫组化染色强。Fas、Fas配体、caspase 3、caspase 9、Bax、Apaf-1和bcl-2在破碎红纤维上也有表达。在包涵体肌炎和边缘空泡型远端肌病中，Fas在空泡样纤维中表达增高。其发病机制可能与Fas相关的细胞凋亡有关。在多发性肌炎，然而，Fas不表达。另一方面，在皮肌炎中，tenacin在间质区以网络图案染色。Tenacin也显示束周萎缩。Tenacin是诊断皮肌炎的一个非常有用的标志物，本研究检测了心肌毒素诱导的大鼠骨骼肌坏死后再生肌中抗肌萎缩蛋白（dystrophin）、α-肌聚糖（α-sarcoglycan）、β-肌萎缩蛋白聚糖（β-dystropglycan）、α1-突触营养蛋白（α1-syntrophin）和nNOS的表达。再生过程从基底膜侧向肌膜下侧推进，从与基底膜结构相关的蛋白质向与信号传导相关的蛋白质推进。nNOS的表达与肌纤维类型分化有关，其作用与肌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.