姜黄素对神经病理性痛大鼠脊髓背角及背根神经节神经元大麻素受体1和NR2B表达的影响

Effect of curcumin on expression of cannabinoid receptor 1 and NR2B in spinal cord dorsal horn and dorsal root ganglion neurons in a rat model of neuropathic pain

目的探讨姜黄素对神经病理性痛大鼠脊髓背角及背根神经节（DRG）神经元大麻素受体1（CBR1）及含NR2B亚基N-甲基-D-天冬氨酸（NMDA）受体表达的影响。方法雄性SD大鼠72只，体重200～230g，采用随机数字表法，将其随机分为4组（n=18）：假手术组（s组）、慢性压迫性损伤组（CCI组）、姜黄素组（Cur组）和溶媒对照组（sc组）。S组仅分离、暴露坐骨神经，其余3组采用慢性压迫性损伤法制备神经病理性痛模型。Cur组术后腹腔注射姜黄素100mg·kg-1·d-1，连续14d，SC组给予等容量二甲基亚砜。分别于术前2d、术后1,3、7、10、14d时测定机械缩足反应阈值（MWT）和热缩足潜伏期（TWL）。分别于术后3、7、14d时处死6只大鼠，取脊髓背角和DRG，采用免疫组化法检测神经元CBR1和NR2B的表达。结果与S组比较，其他3组术后MWT降低，TWL缩短，脊髓背角和DRG神经元CBR1和NR2B表达上调（P〈0．05）；与CCI组比较，Cur组术后MWT升高，TWL延长，脊髓背角和DRG神经元CBR1表达上调，NR2B表达下调（P〈0．05），SC组上述指标差异无统计学意义（P〉0．05）。结论姜黄素可减轻大鼠神经病理性痛，其机制与脊髓背角及DRG神经元CBR1表达上调、NR2B表达下调有关。

Objective To investigate the effect of curcumin on the expression of cannabinoid receptor 1 （CBR1） and NR2B subunit-containing NMDA receptor in spinal cord dorsal horn and dorsal root ganglion （DRG） neurons in a rat model of neuropathic pain. Methods Seventy-two male Sprague-Dawley rats, weighing 200-230 g, were randomly divided into 4 groups （ n = 18 each） ： sham operation group （S group）, chronic constrictive injury （CCI） group, curcumin group （Cur group） and solvent control group （SC group）. Neuropathie pain was induced by CCI. The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals in groups CCI, Cur and SC. Cureumin was injected intraperitoneally at 100 mg＂ kg-l . d-1 for 14 consecutive days after operation in Cur group, while the equal volume of dimethyl sulfoxide was given instead of curcumin in SC group. Mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） were measured on 2 days before operation and on 1, 3, 7, 10 and 14 days after operation. Six rats in each group were sacrificed on 3, 7 and 14 days after operation and the lumbar segments of the spinal cord （L4-5） and DRGs were removed to determine the expression of CBR1 and NR2B by immuno-histochemistry. Results Compared with S group, MWT was significantly decreased, TWL was significantly shortened, and the expression of CBR1 and NR2B in spinal cord dorsal horn and DRG neurons was up-regulated after operation in the other three groups （P 〈 0.05）. Compared with CCI group, MWT was significantly increased, TWL was significantly prolonged, the expression of CBR1 in spinal cord dorsal horn and DRG neurons was up-regulated, and the expression of NR2B in spinal cord dorsal horn and DRG neurons was down-regulated after operation in group Cur （P 〈 0.05）, and no significant change in the parameters mentioned above was found in group SC （ P 〉 0.05）. Conclusion Cureumin can alleviate neuropathic pain in rats, and up-regulation of CBR1 expression and down-regulation of NR2B expression in spinal cord dorsal horn and DRG neurons are involved in the mechanism.