单侧外周伤害性刺激诱发大鼠脊髓中转录因子CREB的双侧磷酸化(英文)  

BILATERAL PHOSPHORYLATION OF TRANSCRIPTION FACTOR CREB IN RAT SPINAL CORD INDUCED BY UNILATERAL PERIPHERAL NOXIOUS STIMULI

作　　者：张瑞新[1] 聂红[1] 祁金顺[1] 乔健天[1] 

机构地区：[1]山西医科大学神经生物学研究室,太原030001

出　　处：《神经解剖学杂志》2002年第1期1-7,W001-W002,共9页Chinese Journal of Neuroanatomy

摘　　要：c AMP反应成分结合蛋白 (c AMP response elem ent-binding protein,CREB)是一种转录因子 ,它在磷酸化之后可调节靶基因的转录。 CREB在 13 3位置的丝氨酸的磷酸化 ,与脊髓中伤害性传入的处理有关 ,本文作者等用特殊抗体对此进行了免疫细胞化学研究。在正常大鼠 ,虽然几乎所有脊髓神经元的核中都可见 CREB的轻度着色 ,但磷酸化的 CREB仅见于双侧腰段脊髓的 ～ 层 (75± 15 vs60± 18)和 层 (9± 3 )。用福尔马林注射引起一侧后脚掌出现炎症时 ,可在双侧腰段脊髓看到磷酸化CREB细胞核的快速 (小于 5 min)和节段性的显著增多 ;它们主要分布在双侧背角表层 ～ 层 (2 5 4± 2 0 vs 2 62± 2 3 )、 层(115± 13 )和双侧 ～ 层 (3 46± 2 0 vs3 2 8± 2 6) ;而在对照和炎症组大鼠的胸段脊髓中均未见磷酸化 CREB的增加。在注射CFA诱发一侧炎症或切断一侧坐骨神经的实验组大鼠 ,也可看到至少延续到第三天的强而双侧性的 CREB的磷酸化。这种由一侧后肢伤害性传入引致腰段脊髓中镜像式双侧 CREB磷酸化的出现 ,与一般看到的损伤传入只在同侧脊髓背角引起某些神经化学改变的结果不同 。The cAMP response element binding protein (CREB) is a transcription factor, that regulates the transcription of target genes after being phosphorylated. Phosphorylation of CREB at serine 133 in reference to spinal processing of noxious inputs was studied by immmunocytochemistry with a specific antibody. In naive rats, the weakly stained phosphorylated CREB immunoreactive nuclei were found only in laminae Ⅰ～Ⅱ in either side of lumbar spinal cord (75±15 vs 60±18) and lamina X (9±3), while the CREB immunoreactive nuclei were localized in almost each neuron of the spinal cord. Unilateral hindpaw inflammation, induced by formalin, significantly produced a rapid (< 5 min), segmental and bilateral phosphorylation of CREB in lumbar spinal cord as compared to that in naive and saline control animals. The increased phosphorylated CREB immunoreactive nuclei mainly distributed in superficial laminae Ⅰ～Ⅱ (254±20 vs262±23), lamina Ⅹ (115±13) and laminae Ⅴ～Ⅷ (346±20 vs 328±26). No phosphorylated CREB immunoreactive nuclei were observed in thoracic spinal cord in both control and inflamed rats. Complete Freund's adjuvant induced unilateral inflammation and unilateral sciatic nerve section also resulted in a strong and bilateral phosphorylation of CREB, which lasted for at least three days (the longest time we studied). The result, mirror phosphorylation of CREB in both sides of lumbar spinal cord induced by unilateral noxious inputs originating from hindpaw, suggests a possible central mechanism(s) for the contralateral 'mirror image' hyperalgesia as described in nerve injured humans and experimental animals.

关 键 词：单侧外周伤害性刺激 大鼠 脊髓 转录因子 CREB 双侧磷酸化 磷酸化CREB 痛觉过敏 福尔马林试验 弗氏佐剂 坐骨神经切断 疼痛 

分 类 号：R363[医药卫生—病理学]