脂多糖对脊髓前角运动神经元的损伤作用  

Lipopolysacchride-induced Motor Neuron Injury in the Anterior Horn of Spinal Cord

作　　者：李彬[1] 董惠[1] 李哲[1] 卜晖[1] 刘晓云[1] 孙萌萌[1] 李春岩[1] 

机构地区：[1]河北医科大学第二医院神经内科,石家庄050000

出　　处：《细胞生物学杂志》2008年第1期114-120,共7页Chinese Journal of Cell Biology

基　　金：国家自然科学基金资助项目(No.30670732)~~

摘　　要：研究脂多糖(LPS)诱导的炎症反应对运动神经元的损伤作用及其机制。采用SD乳鼠脊髓器官型培养,分为单纯培养液组和不同浓度LPS组,应用免疫组化、酶活性测定、电镜等技术衡量神经元损伤程度。对LPS组分别给予细胞内钙离子螯合剂BAPTA-AM和NADPH氧化酶抑制剂apocynin,观察运动神经元数量和形态变化。结果显示LPS可以引起剂量和时间依赖性的运动神经元数量减少和培养液中乳酸脱氢酶含量增高,运动神经元超微结构改变明显,中间神经元损伤相对较轻。运动神经元缺乏钙网膜蛋白表达,而BAPTA-AM减轻运动神经元损伤,提示钙离子缓冲能力较低是其较易受损的原因之一。LPS可以引起NADPH氧化酶活性增高,而apocynin对LPS引起的运动神经元丢失有保护作用,说明NADPH氧化酶在炎症介导的运动神经元损伤中发挥着关键作用。The present study was undertaken to investigate the mechanisms involved in lipopolysaccharide （LPS）-induced motor neuron injury. Organotypic spinal cord slice cultures were treated with medium alone or LPS with different concentrations. Neuron injury was measured using immunohistochemistry, enzyme activity assay and electromicroscopy. In addition, LPS group was treated with BAPTA-AM and apocynin respectively, and motor neuron survival was evaluated by SMI-32 immunohistochemistry. The results showed that LPS could induce doseand time-dependent loss of motor neurons and elevation of LDH concentrations in the culture medium. The ultrastructure of motor neurons showed obvious changes. In contrast, interneurons in the dorsal horn were impaired slightly. Motor neuron lacked the expression of calretinin, and BAPTA-AM ameliorated motor neuron injury, indicating that the low capacity of Ca^2＋ buffering is one of the factors responsible for the vulnerability of motor neurons. NADPH oxidase was activated upon LPS challenge and apocynin had neuroprotective potential on LPS-induced motor neuron death, suggesting that NADPH oxidase may play an important role in inflammation-mediated motor neuron injury.

关 键 词：肌萎缩侧索硬化 器官型培养 脂多糖 运动神经元 NADPH氧化酶 

分 类 号：Q42[生物学—神经生物学]