炎症后内脏高敏感大鼠前扣带回皮质NR2A、NR2B表达变化

背景:研究显示N-甲基-D-天冬氨酸(NMDA)受体参与了伤害性信号的传递,中枢前扣带回皮质(ACC)在内脏高敏感大鼠内脏疼痛反应的调节中起重要作用,该作用是由NMDA受体活性增强介导的。目的:检测炎症后内脏痛觉过敏大鼠ACC区域NMDA受体亚基NR2A、NR2B的表达变化,探讨两者在炎症后内脏高敏感形成中的作用。方法:以去氧胆酸结肠灌注建立炎症后内脏痛觉过敏大鼠模型。造模3周后观察实验组和对照组结肠组织病理学改变,以对结直肠扩张(CRD)的内脏运动反射(VMR)幅值为指标评价内脏痛敏感性的变化,以免疫荧光法和蛋白质印迹法检测ACC区域NR2A、NR2B表达情况。结果:实验组和对照组大鼠结肠组织均未见明显病理学改变。CRD压力为60 mm Hg(伤害性刺激)时,实验组VMR幅值显著高于对照组(P0.05)。与对照组相比,实验组ACC区域NR2A、NR2B荧光强度和蛋白表达量均显著上调(P0.05)。结论:ACC区域NMDA受体亚基NR2A、NR2B表达上调在炎症后内脏高敏感的形成中发挥重要作用。

Changes of Expressions of NR2A and NR2B in Anterior Cingulate Cortex of Post-inflammatory Visceral Hypersensitive Rats

Background： It is reported that N-methyl-D-aspartate （NMDA） receptor is involved in the transmission of nociceptive signals. Anterior cingulate cortex （ACC） plays a critical role in the modulation of visceral pain response in visceral hypersensitive rats, and the process is mediated by enhanced activity of NMDA receptor. Aims： To investigate the changes of expressions of NR2A and NR2B, the subunits of NMDA receptor, in ACC of post-inflammatory visceral hyperalgesia rats, and the potential roles of NR2A and NR2B in post-inflammatory visceral hypersensitivity. Methods： Deoxycholic acid was instilled into the rat colon to induce post-inflammatory visceral hyperalgesia. Three weeks after the establishing of model, colonic histopathological changes were observed in both the model group and control group. Magnitude of visceromotor response （VMR） to colorectal distention （CRD） was used to measure the change of visceral pain perception. Expressions of NR2A and NR2B in ACC were determined by immunofluorescence staining and Western blotting. Results： No pathological changes were observed in colonic tissue of rats in both the model group and control group. Magnitude of VMR to noxious CRD （60 mm Hg） was significantly higher in model group than in control group （P〈 0.05）. Both the NR2A and NR2B fluorescence intensities and protein expressions in ACC were significantly higher in model group than in control group （P〈0.05）. Conclusions： Overexpression of NMDA receptor subunits NR2A and NR2B in ACC might play an important role in the formation of post-inflammatory visceral hypersensitivity.