Sekiya Michiko, Ichiyanagi Takashi, Ikeshiro Yasumasa, Yokozawa Takako
Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Japan.
Biol Pharm Bull. 2009 Mar;32(3):382-8. doi: 10.1248/bpb.32.382.
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by the selective loss of motor neurons. There is no effective treatment or drug against ALS, and the precise mechanisms leading to the selective loss of motor neurons are still unknown. We investigated the effect of a Chinese prescription, Wen-Pi-Tang, on the ALS model mouse SOD1(G93A). Although the oral administration of Wen-Pi-Tang extract to SOD1(G93A) mice had no significant effect on body weight loss and survival time, Wen-Pi-Tang delayed disease onset. Therefore, we evaluated immunohistological changes in the spinal cord of SOD1(G93A) mice during the early disease period, and found that Wen-Pi-Tang extract inhibited neuronal loss in the lumbar segment of the spinal cord of mice. Furthermore, increased astrocytes and microglial cells, which increase prior to neuronal loss, in spinal cords were significantly reduced in the Wen-Pi-Tang treated group. Since oxidative markers, heme oxygenase-1 and inducible nitric oxide synthase, in the spinal cord were also reduced as well as the change in microglia, the administration of Wen-Pi-Tang was thought to delay disease onset by inhibiting glial cell activation.
肌萎缩侧索硬化症(ALS)是一种成年发病的神经退行性疾病,其特征是运动神经元选择性丧失。目前尚无针对ALS的有效治疗方法或药物,导致运动神经元选择性丧失的确切机制仍不清楚。我们研究了中药方剂温脾汤对ALS模型小鼠SOD1(G93A)的影响。虽然给SOD1(G93A)小鼠口服温脾汤提取物对体重减轻和存活时间没有显著影响,但温脾汤延迟了疾病发作。因此,我们评估了SOD1(G93A)小鼠疾病早期脊髓的免疫组织学变化,发现温脾汤提取物可抑制小鼠脊髓腰段的神经元丢失。此外,在温脾汤治疗组中,脊髓中在神经元丢失之前增加的星形胶质细胞和小胶质细胞显著减少。由于脊髓中的氧化标志物血红素加氧酶-1和诱导型一氧化氮合酶也随着小胶质细胞的变化而减少,因此认为温脾汤的给药通过抑制胶质细胞活化来延迟疾病发作。