Ikeda K, Kinoshita M, Iwasaki Y, Tagaya N, Shiojima T
Fourth Department of Internal Medicine, Toho University Ohashi Hospital, Tokyo, Japan.
Neuromuscul Disord. 1995 Sep;5(5):383-90. doi: 10.1016/0960-8966(95)00003-6.
Gene mutations of Cu/Zn superoxide dismutase (SOD) have been discovered in familial amyotrophic lateral sclerosis (ALS). Oxidative stress also plays a role in the pathogenesis of sporadic ALS. Whether antioxidant therapy is beneficial in this fatal disease is now crucial. We have shown that SOD treatment improves neuromuscular dysfunction and morphological changes in wobbler mouse motoneuron disease. Progressive spinal motor neuronopathy and axonopathy, predominantly in the cervical cord, occur at postnatal age 3-4 weeks, leading to muscle weakness and contracture of the forelimbs in this animal. These motor deficits rapidly increase by postnatal age 6-8 weeks, and then slowly progress. Wobbler mice were given two doses daily of phosphatidyl choline-bound Cu/Zn SOD (PC-SOD, 10(4), 10(5) U/kg) or a vehicle solution by intraperitoneal injection from postnatal 3-4 to postnatal 7-8 weeks of age. PC-SOD treatment attenuated progression of motor dysfunction, prevented denervation muscle atrophy, and delayed degeneration of spinal motoneurons in wobbler mice. This raises the possibility that PC-SOD may have therapeutic potential in human motoneuron disease.
在家族性肌萎缩侧索硬化症（ALS）中已发现铜/锌超氧化物歧化酶（SOD）的基因突变。氧化应激在散发性ALS的发病机制中也起作用。抗氧化治疗对这种致命疾病是否有益目前至关重要。我们已经表明，SOD治疗可改善震颤小鼠运动神经元疾病中的神经肌肉功能障碍和形态学变化。进行性脊髓运动神经元病和轴索性神经病主要发生在颈髓，在出生后3 - 4周出现，导致该动物前肢肌肉无力和挛缩。这些运动缺陷在出生后6 - 8周迅速增加，然后缓慢进展。从出生后3 - 4周到出生后7 - 8周，每天给震颤小鼠腹腔注射两剂磷脂酰胆碱结合的铜/锌SOD（PC - SOD，10⁴、10⁵ U/kg）或赋形剂溶液。PC - SOD治疗减轻了运动功能障碍的进展，预防了失神经肌肉萎缩，并延缓了震颤小鼠脊髓运动神经元的退化。这增加了PC - SOD在人类运动神经元疾病中可能具有治疗潜力的可能性。
