脊髓背角N-甲基-D-天冬氨酸受体在结肠炎大鼠内脏高敏感性中的作用

目的：通过观察大鼠结肠炎不同时期脊髓背角N-甲基-D-天冬氨酸受体（NMDAR）的表达，探讨突触后NMDAR在内脏高敏感性中的作用。方法：成年雄性Sprague-Dawley（SD）大鼠70只，随机分为实验组和对照组。实验组大鼠用三硝基苯磺酸（TNBS）灌肠诱导结肠炎。对照组大鼠用生理盐水灌肠。分别在灌肠后3，7，14和28d记录结肠球囊扩张下大鼠腹壁肌电活动；应用荧光免疫组织化学法观察脊髓背角NMDAR1和NMDAR2A/B的表达。结果：TNBS灌肠后3，7和14d，实验组大鼠腹肌收缩次数明显多于对照组（P<0.05）；TNBS灌肠后28d，实验组中仍有部分大鼠（2/7）腹肌收缩明显增多。TNBS灌肠后7d和14d，脊髓背角NMDAR1和NMDAR2A/B阳性细胞数明显多于对照组（P<0.05）；TNBS灌肠后28d，部分大鼠（4/7）脊髓背角深层仍有多量的NMDAR1和NMDAR2A/B阳性细胞，其计数明显多于对照组（P<0.05）。结论：NMDAR在内脏伤害性信息转导中起作用；结肠炎恢复后脊髓背角NMDAR1和NMDAR2A/B的同步上调是导致内脏敏感性持续增高的原因。

Effects of N-methyl-D-aspartate receptor in visceral hypersensitivity in rats with colonic inflammation

Objective To investigate the effects of N-methyl-D-aspartate receptor (NMDAR) in the spinal dorsal horn in visceral hypersensitivity in rats with colonic inflammation. Methods Seventy adult male Sprague-Dawley (SD) rats were randomly divided into the experimental group and the control group. Colonic inflammation was induced in the experimental rats by intraluminal administration of trinitrobenzenesulfonic acid (TNBS). Saline was administered intraluminally in the control rats. After 3, 7, 14, and 28 days of administration, abdominal contractions induced by inflation of a balloon colonically inserted were recorded in rats by implanting electrodes in the abdominal striated muscles. Immunohistochemistry method was used to study the expression of NMDAR1 and NMDAR2A/B in lumbarsacral spinal cord following after inflammation. Results Colonic distension evoked a significant increase of abdominal contractions after 3, 7 and 14 days of TNBS administration. After 28 days of TNBS administration, abdominal contractions were still significantly increased in 2 TNBS-treated rats compared with the control rats. After 7 and 14 days of TNBS administration, NMDAR1 and NMDAR2A/B-immunoreactive cells were significantly increased compared with the control group (P<0.05). Twenty-eight days after TNBS administration, the number of NMDAR1-IR and NMDAR2A/B-IR neurons was still significantly increased in 4 TNBS-treated rats compared with the saline-treated rats (P<0.05). Conclusion NMDAR was involved in the transmission of visceral nociceptive stimuli. After the remission of colonic inflammation, increased expression of NMDAR1 and NMDAR2A/B in the spinal dorsal horn may induce persistent neuronal hyperactivity, which results in visceral hypersensitivity.