Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Liaoning Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.
CNS Neurosci Ther. 2017 May;23(5):375-385. doi: 10.1111/cns.12681. Epub 2017 Feb 22.
To evaluate the therapeutic effects of n-butylidenephthalide (BP) in SOD1 mouse model of amyotrophic lateral sclerosis and explore the possible mechanisms.
The SOD1 mice were treated by oral administration of BP (q.d., 400 mg/kg d) starting from 60 days of age and continuing until death. The rotarod test was performed to assess the disease onset. The expression levels of apoptosis-related proteins, inflammatory molecules, and autophagy-associated proteins were determined. The number of apoptotic motor neurons and the extent of microglial and astroglial activation were also assessed in the lumbar spinal cords of BP-treated mice. Grip strength test, hematoxylin-eosin staining, nicotinamide adenine dinucleotide hydrogen staining, and malondialdehyde assay were conducted to evaluate the muscle function and pathology.
Although BP treatment did not delay the disease onset, it prolonged the life span and thereafter extended the disease duration in SOD1 mouse model of ALS. BP treatment also reduced the motor neuron loss through inhibiting apoptosis. We further demonstrated that the neuroprotective effects of BP might be resulted from the inhibition of inflammatory, oxidative stress, and autophagy.
Our study suggests that BP may be a promising candidate for the treatment of ALS.
评估丁基苯酞（BP）在肌萎缩侧索硬化症 SOD1 小鼠模型中的治疗效果，并探讨可能的机制。
从 60 日龄开始，SOD1 小鼠通过口服 BP（q.d.，400mg/kg/d）进行治疗，直至死亡。通过转棒试验评估疾病发作情况。测定凋亡相关蛋白、炎症分子和自噬相关蛋白的表达水平。还评估了 BP 治疗小鼠腰椎脊髓中凋亡运动神经元的数量以及小胶质细胞和星形胶质细胞的激活程度。握力试验、苏木精-伊红染色、烟酰胺腺嘌呤二核苷酸氢染色和丙二醛测定用于评估肌肉功能和病理学。
尽管 BP 治疗并未延迟疾病发作，但它延长了 SOD1 肌萎缩侧索硬化症小鼠模型的寿命，并在此后延长了疾病持续时间。BP 治疗还通过抑制凋亡减少了运动神经元的丢失。我们进一步证明，BP 的神经保护作用可能源于对炎症、氧化应激和自噬的抑制。
我们的研究表明，BP 可能是治疗肌萎缩侧索硬化症的有前途的候选药物。
