金荞麦总黄酮下调NR2B表达改善IBS大鼠痛觉过敏

Improvement of IBS rats'hyperalgesia by total flavones of Fagopyrum cymosum via down-regulation of NR2B expression

目的观察金荞麦总黄酮(Fag)对IBS样结肠刺激大鼠模型(CI模型)内脏敏感性的改善作用和对模型脊髓后角和海马内NMDA受体亚基NR2A、NR2B的影响。方法采用结肠刺激新生期乳大鼠法来制作IBS样CI模型。CI大鼠成年后给予口服Fag 2周,并用腹壁撤退反射(AWR)评分评价给药后CI大鼠内脏高敏感性的变化,用免疫组化法和蛋白印迹法进一步观察其脊髓后角和海马内NMDA受体亚基NR2A、NR2B的变化。结果和对照组比,CI组AWR评分明显增高,而高剂量Fag明显降低CI组的AWR评分。对照组脊髓后角、海马均可见NR2A、NR2B亚基表达,但CI组只有NR2B亚基表达增强,且高剂量Fag可降低其表达,NR2A亚基表达在各组变化不大。结论 Fag通过下调致敏中枢上脊髓后角和海马的NR2B表达对IBS样CI大鼠的痛觉过敏有改善作用。

Aim To investigate the therapeutic effects of total flavones of Fagopyrum cymosum （Fag） on visceral hypersensitivity in IBS-like colon irritation （CI） in rats, and on the expression of NR2A and NR2B, two subunits of NMDA receptor, in spinal dorsal horn and hippocampus. Methods Neonatal CI method was used to establish IBS-like rat models. Adult CI rats were given Fag by mouth for 2 weeks. Abdominal withdrawal reflex （AWR） scoring system was employed to evaluate the visceral hypersensitivity. The expression of NR2A and NR2B submits in both spinal cord dorsal horn and hippocampus was determined by immunohistochemistry and western blot. Results AWR scores of CI rats were significantly increased compared with thatof control rats; whereas Fag at high dose could markedly reduce AWR scores in CI rats. Moreover, expression of NR2A and NR2B subunits in both spinal dorsal horn and hippocampus was observed in control rats. In CI rats only NR2B expression was increased and it could be reduced by Fag at high dose. No signif- icant alteration in NR2A expression was observed between groups. Conclusions Fag exerts therapeutic effects on hyperalgesia in IBS-like CI rats through down-regulation of NR2B expression in both spinal cord dorsal horn and hippocampus of sensitized CNS.