摘要
研究二相酶诱导剂3H-1,2-dithiole-3-thione(D3T)对体外培养的运动神经元的保护作用。选用生后7天的SD乳鼠脊髓腰段切成薄片进行体外培养,正常培养1周后分组干预,对照组只加入正常培养液,THA组于培养液中加入谷氨酸转运体抑制剂threo-hydroxyaspartate(THA),D3T48h+THA组于培养液中加入不同浓度的D3T,48h后同时给予THA和相应浓度的D3T。D3T+THA组于培养液中同时给予THA和不同浓度的D3T。培养4周后观察运动神经元数量和超微结构变化。另外对培养1周后的脊髓薄片给予不同浓度的D3T,观察D3T干预48h后运动神经元数量与相应对照组之间的差异。结果显示D3T对THA引起的运动神经元的丢失有保护作用,且能够减轻THA引起运动神经元超微结构损害。由此认为,二相酶诱导剂D3T有望成为肌萎缩侧索硬化治疗的新切入点。
In this study, we want to investigate the role of phase Ⅱ enzyme inducer 3H-1,2-dithiole-3-thione （D3T） on motor neuron survival. The organotypic spinal cord cultures were prepared from 7 day old rat pup lumbar spinal cords. Lumbar spinal cords were collected under sterile conditions, sectioned transversely at 350 μm intervals. Slices were placed on the inserts. After 1 week in culture, the threo-hydroxyaspartate （THA） group, treated with THA alone to achieve a final concentration of 100 μmol/L. For the D3T48h＋THA group, tissues were treated with D3T to achieve a final concentration of 15, 30 μmol/L, 48 hour later, the same concentration D3T and 100 μmol/L THA were added to the medium. For the D3T＋THA group, tissues were treated with D3T to achieve a final concentration of 15, 30 μmol/L and 100 μmol/L THA were added simultaneously. 0.1%DMSO was added to the drug solubilizer control, no drugs added to the control group. After 4 weeks in culture, tissue were harvested, the number of motor neurons and the ultrastructure of motor neuron were observed by immunohistochemistry and electromicrography. We also compared D3T48h （add D3T 48 h after 7 day culture） group with control （no drug add after 7 day culture） by counting the number of motor neuron. The results showed that D3T can prevent THA-induced motor neuron death, increase motor neuron survival. It suggested that D3T have neuroprotective potential on THA-induced motor neuron death. Phase Ⅱ enzyme inducer may provide a novel neuroprotective strategy for the treatment of amyotrophic lateral sclerosis.
出处
《细胞生物学杂志》
CSCD
2007年第1期135-139,共5页
Chinese Journal of Cell Biology
基金
河北省自然科学基金资助项目(No.303487)~~
关键词
萎缩侧索硬化
D3T
运动神经元
脊髓
amyotrophic lateral sclerosis
3H-1,2-dithiole-3-thione
motor neuron
spinal cord
