生酮饮食对颈脊髓损伤大鼠功能预后及神经保护作用的研究

关键词：脊髓损伤  生酮饮食  行为学评估  神经保护  功能恢复

Keywords:spinal cord injury  ketogenic diet  behavioral assessment  neuroprotection  functional recovery

摘要：

      摘要 目的：探索生酮饮食对脊髓损伤大鼠功能预后的影响及神经保护机制在其中所起的作用。 方法：对SD大鼠经过充分的行为学训练后，利用IH脊髓打击器建立SD大鼠单侧C5脊髓不完全损伤模型。术后将动物分为两组，分别给予普通标准饮食（standard diet，SD）和生酮饮食（ketogenic diet，KD），术后第4、7天及此后每周监测血β-羟丁酸水平，每2周进行1次行为学评估（Staircage实验和Rearing实验）。8周后将动物处死，取损伤部位的脊髓组织进行连续冰冻切片EC染色，镜下观察并测量损伤部位灰质和白质的残存量。 结果：在术后观察的8周内，KD组从术后第3天开始尾静脉血β-羟丁酸水平显著增高，维持在1.5mmol/L以上（最高2.89mmol/L）；SD组血酮水平维持在0.70mmol/L左右。术后2周时SD组与KD组Staircage得分差异无显著性，术后4、6及8周时KD组得分均明显高于SD组；术后2、4、8周时KD组Rearing得分明显高于SD组，术后6周KD组与SD组得分差异虽无显著性，但两组均值差别趋势仍较明显（P=0.07）；KD组损伤部位灰质/白质残存量均明显多于SD组。 结论：生酮饮食对脊髓损伤后神经功能有保护作用，可能是通过保留残存神经组织量的途径实现。

Abstract:

      Abstract Objective: To investigate whether a restricted KD regimen can result in improvement of functional outcomes and neuroprotection in rats after spinal cord injury. Method: Immediately after C5 hemi-contusion injury, 34 Sprague-Dawley rats were fed with either standard diet (SD, ad libitum) or a restricted ketogenic diet (KD). Blood β-hydroxybutyrate concentration and forelimb function were evaluated for 8 weeks, followed by quantitative assessment of spinal cord tissue sparing using EC staining. Result: Blood β-hydroxybutyrate concentration in KD group remained above 1.50mmol/l during the 8 weeks without decrease (maximal level 2.89 mmol/l). The blood β-hydroxybutyrate concentration in SD group was around 0.70 mmol/l. Staircage scores of KD and SD groups were similar at 2 weeks post injury, but then KD group got significantly higher scores than SD group in the later assessments. Rearing scores of KD group were significantly higher than SD group at 2 weeks, 4 weeks and 8 weeks after injury, although no significant difference was found between the two groups at 6 weeks after injury with the P value very closed to 0.05 (P=0.07). There was much more gray/white matter sparing in KD group than in SD group. Conclusion: Ketogenic diet can improve the recovery of forelimb function in animals with spinal cord injury. This therapeutic effect of ketogenic diet may be attributed to the protection of tissue sparing.