目的探讨成人散发起病的下运动神经元病(lower motor neuron disease,LMND)患者铜锌超氧化物歧化酶1(superoxide dismutase 1,SOD1)基因、运动神经元存活基因(survive motor neuron,SMN)及雄激素受体(androgen receptor,AR)基因对明确诊断疾病类型的作用。方法收集43例成人散发起病表现为LMND的患者取外周血提取基因组DNA,分别进行聚合酶链式反应(PCR)扩增SOD1基因外显子1-5,SMN基因外显子7及男性LMND患者AR基因外显子1,对产物进行高分辨熔解曲线分析、变性聚丙烯酰胺凝胶电泳分析及测序。结果在43例成年LMND患者中,未发现SOD1基因突变。2例男性患者有SMN1外显子7的纯合缺失,诊断为Ⅲ、Ⅳ型脊髓性肌萎缩(SMA)。在31例男性患者中发现3例AR基因外显子1的CAG三核苷酸重复序列数分别为49、50、52,可诊断肯尼迪病。结论对LMND患者进行SMN1基因外显子7及AR基因外显子1检测,可使部分散发或无明确家族史的患者明确诊断,并可对病情及预后进行评估。
Background Amyotrophic lateral sclerosis （ALS） is a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Transgenic mice over-expressing a mutant form of the human SOD1 gene develop an ALS-like phenotype. Currently, there is no effective treatment or drug for the fatal disease. Previous studies reported potent efficacy of dl-3-n-butylphthalide （DL-NBP） for several neurodegenerative disorders and cerebral ischemia. SOD1-G93A mice are a mouse model of ALS. In this study, we investigated the efficacy of DL-NBP on this ALS mouse model. Methods Sixty SOD1-G93A female mice were divided into four groups. The vehicle control group received 0 mg.kg-1.d-~ DL-NBP. The experimental groups received DL-NBP with doses of 30, 60 or 120 mg.kgl.d1, respectively. For measurement of motor activity, the hanging wire test and rotarod test were performed. Survival statistics were analyzed by Kaplan-Meier survival curves. The body weight of each mouse was recorded twice per week. The statistical motor unit number estimation （MUNE） technique was used to estimate the number of functioning motor units in gastrocnemius muscle. Muscle morphology was evaluated by hematoxylin and eosin staining. Motor neuron quantJtation was performed by Nissl staining and microglia activation was observed by immunohistochemistry. Results Oral administration of 60 mg.kg-l-d-1 DL-NBP significantly prolonged survival （（164.78±16.67） days） of SOD1-G93A mice compared with vehicle control （（140.00＋16.89） days）. Treating mice with DL-NBP （60 mg.kg-1.d-1） significantly decreased the progression rate of motor deficits and suppressed body weight reduction. Furthermore, we found that treating SOD1-G93A mice with DL-NBP （60 mg.kgl.d1） slowed the rate of MUNE reduction （P 〈0.01）. Motor neurons were remarkably preserved in the anterior horns in mice treated with DL-NBP （60 mg.kg-1d-1） at the stage of 19 weeks （P 〈0.01）. Treating mice with DL-NBP （60 mg.kg1.d1） si
