前扣带回NMDA受体NR2A亚单位与睡眠剥夺模型大鼠外周疼痛感受阈值的关系被引量：1

Role of NR2A receptor of anterior cingulate cortex in the thermal hyperalgesia of sleep deprivation rats

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摘要目的观察睡眠剥夺(SD)模型大鼠外周疼痛感受阈值的改变及其中枢痛觉感受区域前扣带回兴奋性谷氨酸受体(NMDA)的表达变化。方法 80只雄性SD大鼠随机均分为4组:正常对照(Con)组,睡眠剥夺(SD)24h(SD24h)组,SD48h组及SD72h组。采用小平台水环境法制作睡眠剥夺大鼠模型,采用热敏测试仪测定各组大鼠足底热刺激缩足潜伏期以反映足部热痛阈值的变化。同时采用Westernblotting和免疫荧光技术检测大鼠脑组织皮质前扣带回NR2A和NR2B蛋白的表达。结果 SD48h组及SD72h组大鼠热刺激缩足潜伏期分别为6.87±1.56s和5.18±1.15s,较对照组Con组(8.08±1.86s)有明显降低(P<0.05),而SD24h组(7.97±1.58s)与对照组无明显差异。Westernblotting检测结果显示,SD48h、SD72h组大鼠脑组织ACC区域NR2A蛋白表达(0.52±0.12,0.57±0.13)较Con组(0.41±0.12)有明显上调(P<0.05),SD24h组(0.43±0.14)与对照组比较无显著性差异;而NR2B的蛋白在各组间的表达(SD24h组、SD48h组、SD72h组和Con组依次为0.68±0.19、0.76±0.18、0.74±0.16和0.74±0.19)的NR2B表达无显著差异。免疫荧光检测结果显示,与Con组(12.04±3.17)比较,SD48h组(15.19±3.56)及SD72h组(16.1±3.88)NR2A表达明显上调(P<0.01),SD24h组(12.59±2.79)无显著差异。NR2B蛋白在各组间的表达(SD24h组、SD48h组、SD72h组和Con组依次为32.51±7.45、34.1±6.78、33.59±5.85、33.04±8.57)无显著差异。结论睡眠剥夺48h和72h后,大鼠足部痛阈下降,同时伴行脑皮质前扣带回区域NMDA受体NR2A亚单位的表达上调。 Objective To investigate the changes in thermal pain threshold of sleep deprivation （SD） rats, that of the expression of NMDA, which is a central pain receptor in anterior cingulate cortex （ACC） of SD rats. Methods Eighty male Sprague-Dawley rats were randomly divided into 4 groups （20 each）： control group （with normal sleep） and 3 sleep deprivation groups （the period of sleep deprivation were 24h, 48h and 72h, respectively）. Sleep deprivation （SD） was achieved by using a narrow platform surrounded with water technique. The change in thermal pain threshold of SD rats＇ paws was observed, and the levels of NR2A and NR2B protein in the ACC were detected with Western blotting and immunofluoreseenee assay. Resets Rats in SD48h and SD72h groups showed increased sensitivity to thermal stimuli on the paws, i.e. the withdrawal lateney was shortened significantly compared with that of the rats in control group [（6. 87±1.56 and 5.18±1. 15s, respectively, vs 8.08±1. 86s, （P〈0. 05）], while the withdrawal latency showed no obvious change in the rats of SD24h group （7. 97 ±1. 58s, P〉0.05）. The expression of NR2A was up -regulated in SD48h and SD72h groups [SD48h （0. 52 ±0. 12, IOD： 15. 19 ±3. 56）, SD72h （0. 57 ± 0. 13, IOD： 16. 1± 3. 88） vs control （0.41 ± 0. 12, IOD： 12. 04 ± 3. 17）, （P〈0. 05）]. However, no significant difference was found in NR2A expression between SD24h group and control group ESD24h （0. 43±0. 14, IOD： 12. 59±2. 79） vs control （0. 41 ±0. 12, IOD.. 12. 04±3. 17）, （P〉0. 05）1. Moreover, no obvious difference was found in NR2B expression among the four groups [SD24h （0. 68 ±0. 19, IOD： 32. 51±7. 45）, SD48 （0. 76±0. 18, IOD： 34. 1±6.78）, SD72h （0. 74 ±0. 16, IOD： 33. 59±5. 85）, vs control （0. 74±0. 19, IOD： 33. 04±8. 57）, （P〉0. 05）]. Conclusion Sleep deprivation for 48h and 72h can lead to thermal hyperalgesia of rats accompanied with the up-regulation of NR2A expression in rat ACC.

作者魏磊高峻吴文彬李桂香李兆申

机构地区第二军医大学长海医院消化内科

出处《解放军医学杂志》 CAS CSCD 北大核心 2010年第10期1235-1237,1241,共4页 Medical Journal of Chinese People's Liberation Army

关键词睡眠剥夺热痛阈扣带回 N-甲基天冬氨酸 sleep deprivation pain threshold gyrus cinguli N-methylaspartate

分类号 R338.63 [医药卫生—人体生理学]

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参考文献8

1Lautenbacher S, Kundermann B, Krieg JC. Sleep deprivation and pain perception[J]. Sleep Med Rev, 2006, 10(5): 357-369.
2Baumbauer KM, Young EE, Joynes RL.Pain and learning in a spinal system: contradictory outcomes from common origins[J]. Brain Res Rev, 2009, 61(2):124-143.
3Perez NM, Benedito MA. Activities of monoamine oxidase (MAO) A and B in discrete regions of rat brain after rapid eye movement (REM) sleep deprivation[J].Pharmacol Biochem Behav, 1997, 58 (2):605- 608.
4Hakki Onen S, Alloui A, Jourdan D, et al. Effects of rapid eye movement (REM) sleep deprivation on pain sensitivity in the rat[J]. Brain Res, 2001, 900(2): 261-267.
5Kundermann B, Spernal J, Huber MT, et al. Sleep deprivation affects thermal pain thresholds but not somatosensory thresholds in healthy volunteers[J]. Psychosom Med, 2004, 66(6): 932-937.
6刘谦,杜亚平,钱伟,侯晓华.REM睡眠剥夺对大鼠内脏感觉影响的研究[J].胃肠病学和肝病学杂志,2006,15(2):134-137. 被引量：8
7Suckow SK, Caudle RM. NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs) during inflammation induced visceral hypersensitivity[J].Mol Pain, 2009, 22(5):54.
8Fan J, Wu X, Cao Z, et al. Up-regulation of anterior clngulate cortex NR2B receptors contributes to visceral pain responses in rats[J]. Gastroenterology, 2009, 136(5): 1732-1740.

二级参考文献18

1Mertz H. Review article : visceral hypersensitivity. Aliment Pharmacol Ther, 2003,17(5) :623-633.
2Clouse B E. Antidepressants for irritable bowel syndrome. Gut, 2003,52(4) :598-599.
3Giedke H.The usefulness of therapeutic sleep deprivation in depression. J Affect Disord, 2004,78(1):85-86.
4Beneclito M. A. C. Camarini R. Rapid eye movement sleep deprivation induces an increase in acetylcholinesterasc activity in discrete rat brain regions. Braz J Med Biol Res, 2001,34(1):103-109.
5Liang LX, Zhang Q, Hou XH. Antinociceptive property of tagaserod in arat model of chronic visceral hypersensitivity. Chin J Dig Dis, 2005, 6 : 21-25.
6AI-Chaer ED, Kawasaki M, Pasricha PJ. A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology, 2000,119(5) : 1276-1285.
7Mertz H, Naliboff B, Munakata J, et al. Altered rectal perception is a biological marker of patiens with irritable bowel syndrome. Gastroenterology,1995, 109(1):40-52.
8De Ponti F. Malagelada J R. Functional Gut Disorders- From Motility to Sensitivity Disorders. A Review of Current and Investigational Drugs for Their Management. Pharmacol Ther, 1998, 80(1):49-88.
9Cirelli C, Tononi G. Gene expression in the brain across the sleep-waking cycle. Brain Res, 2000, 885(2) :303-321.
10Cirelli C. How sleep deprivation affects gene expression in the brain: a review of recent findingS. J Appl Physiol, 2002,92(1):394-400.