胰岛素样生长因子(IGF-1)对体外培养的脊髓和皮层运动神经元的保护作用

Neuroprotective potential of IGF-1 on THA-induced motor neuron death in rat

目的研究胰岛素样生长因子(IGF-1)对THA诱导的运动神经元损伤的保护作用。方法选用生后7d和1d的SD乳鼠,7d龄乳鼠用于脊髓片培养,1d龄乳鼠用于脑片培养。在无菌条件下断头取脊髓腰膨大部分或脑组织,将脊髓腰膨大部分和包含运动皮层的脑组织切成薄片进行体外培养,对照组加入正常培养基,模型组给予谷氨酸转运体抑制剂-THA进行干预,IGF-1组于培养液中同时加入THA和不同浓度的IGF-1。药物干预3w后,应用免疫组织化学方法显示运动神经元并计数。结果 THA能够选择性诱导脊髓前角运动神经元和皮层运动神经元死亡,IGF-1能阻止THA诱导的运动神经元的死亡。结论 IGF-1对THA诱导的慢性运动神经元损伤具有保护作用,IGF-1可能有益于ALS的治疗。

Objective To study the effect of IGF-1 on THA - induced motor neuron death. Methods The organotypic spinal cord and brain slice cultures were prepared from 7 - day - old rat pups＇lumbar spinal cords and 1- day-old rat pups＇brain tissue. The slices were collected under sterile conditions, sectioned transversely at 350 μm in- tervals. The explants were placed on the inserts. After I week in culture for spinal cord slices and 2 weeks for brain slices, the THA group was treated with THA alone to achieve a final concentration of 100μm. For the IGF-1 ＋ THA group, explants were co-treated with IGF-1 to achieve a final concentration of 10 or 25ng/mL, and simultaneously with 100μm THA. No drugs added to the control group. After 3 weeks treatment, the explants were harvested. The number of motor neurons was evaluated by SMI -32 immunostaining. Results THA induced selective motor neuron death. IGF-1 could prevent motor neuron death from chronic THA treatment, and increase motor neuron survival. Conclusion IGF-1 has the neuroprotective potential on THA - induced motor neuron death, and may provide benefit for amyotrophic lateral sclerosis （ALS） treatment.