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

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

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。

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 trini- trobenzenesulfonic 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 eolonically 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 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 NMDARI-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.