右美托咪定对神经病理性痛大鼠脊髓P2X3和P2X4受体表达的影响

摘要：目的  探讨右美托咪定对神经病理性痛大鼠脊髓P2X3和P2X4受体表达的影响。方法  60只健康雄性SD大鼠随机分为假手术组（Sham组）、神经病理性痛组（NP组）和右美托咪定干预组（DI组），复制神经病理性痛大鼠模型。于模型复制即刻，DI组大鼠腹腔注射40μg/kg右美托咪定，间隔24 h给药1次，连续进行至模型复制成功后14 d，Sham组和NP组给予等量生理盐水腹腔注射。分别于复制模型前（T0）、复制模型后24 h（T1）、72 h（T2）、7 d（T3）和14 d（T4），对大鼠机械缩足阈值（MWT）和热缩足潜伏期（TWL）进行测定。Western blot检测大鼠脊髓P2X3和P2X4受体总蛋白及膜蛋白的表达。结果  与Sham组比较，NP组和DI组大鼠T1、T2、T3、T4时MWT和TWL降低；与NP组比较，DI组大鼠T2、T3、T4时MWT和TWL升高，差异有统计学意义（P <0.05）。与Sham组比较，NP组大鼠脊髓P2X3和P2X4受体总蛋白及膜蛋白升高；与NP组相比，DI组大鼠脊髓P2X3和P2X4受体总蛋白及膜蛋白降低，差异有统计学意义（P <0.05）。结论  右美托咪定可有效改善神经病理性痛大鼠痛觉过敏症状，可能与抑制脊髓中P2X3和P2X4受体蛋白的表达有关。

Effects of Dexmedetomidine on expressions of P2X3 and P2X4 receptors in spinal cord of rats with neuropathic pain

Abstract: Objective To investigate the effects of Dexmedetomidine on the expressions of P2X3 receptor and P2X4 receptor in the spinal cord of rats with neuropathic pain. Methods Sixty healthy male SD rats were randomly divided into sham operation group (sham group), neuropathic pain group (NP group) and Dexmedetomidine intervention group (DI group). The neuropathic-pain rat models were constructed. At the start of model construction, the rats in the DI group were intraperitoneally injected with 40 μg/kg Dexmedetomidine, which was repeated at 24-h intervals till 14 d after the models were successfully constructed. The rats in the sham group and the NP group were given intraperitoneal injection of normal saline. Mechanical withdraw threshold (MWT) and thermal withdrawal latency (TWL) of the rats were detected before model construction (T0) and 24 h (T1), 72 h (T2), 7 d (T3) and 14 d (T4) after model construction. The expressions of total proteins and membrane proteins of P2X3 receptor and P2X4 receptor in the spinal cord of the rats were detected using Western blot. Results Compared with the sham group, the MWT and TWL in the NP group and the DI group were decreased at T1-4; compared with the NP group, the MWT and TWL in the DI group were increased at T2-4, the differences were statistically significant (P < 0.05). Compared with the sham group, the expressions of total proteins and membrane proteins of P2X3 receptor and P2X4 receptor in the spinal cord of the rats in the NP group were increased; compared with the NP group, the expressions of total proteins and membrane proteins of P2X3 receptor and P2X4 receptor in the spinal cord of the rats in the DI group were decreased, the differences were statistically significant (P < 0.05). Conclusions Dexmedetomidine could effectively improve the symptoms of neuropathic hyperalgesia in the neuropathic-pain rats. It might be related with the inhibition of the expressions of P2X3 receptor and P2X4 receptor proteins in the spinal cord.