氯胺酮对神经痛大鼠模型海马NR2B亚单位表达的影响

Effect of Ketamine on NR2B subtype expression in hippocampus of neuropathic pain rats

目的研究亚麻醉剂量氯胺酮对神经痛(NP)大鼠模型的镇痛作用及对海马NR2B亚单位的影响。方法采用坐骨神经慢性压迫法(CCI)制备大鼠NP模型。大鼠随机分为4组(n=6):假手术组(SO组)、模型组(NP组)、K1、K2组。K1和K2组于CCI术后7～31 d每天分别腹腔注射氯胺酮10、20 mg/kg。各组分别于术前1 d和术后3、7、21、31 d测定大鼠术侧后爪痛阈;术后第31天,用RT-PCR和Western blot的方法检测大鼠海马组织中NR2B mRNA和蛋白的表达水平。结果与SO组比较,NP、K1组和K2组术后痛阈明显降低(P<0.05),手术对侧海马组织中NR2B表达水平增高(P<0.05)。与NP组比较,K1组和K2组术后痛阈升高(P<0.05),海马的NR2B蛋白表达降低(P<0.05)。结论亚麻醉剂量氯胺酮可以部分反转NP模型痛觉过敏和海马的NR2B亚单位表达增高。

Objective To evaluate the analgesic effect of Ketamine on a rat model of neuropathic pain （NP） and expres sion of NR2B subtype in hippocampus. Methods NP model was prepared by chronic constrictive injury （CCI） of sciatic nerve. Rats were randomly divided into four groups （n = 6）： Sham operation group （SO group）, NP group, K1 group, K2 group. K1 and K2 group were daily intraperitoneally injected ketamine at subanesthetic dose of 10 mg/kg and 20 mg/kg body weight respectively for 7-31 days after CCI operation. Pain thresholds of hind legs of NP rats were mea- sured on the preoperative 1 day and 3, 7, 21, 31 days after operation respectively. On the 31st day, NR2B mRNA and protein expression level in hippocampus was estimated by using RT-PCR and Western blot. Results Compared with SO group, the lin thresholds were reduced significantly in NP, K1, K2 group （P 〈 0.05）; the NR2B expression levels in the contralateral hippocampus were increased （P 〈 0.05） in NP, K1 and K2 groups. Compared with NP group, the pain thresholds were increased in K1, K2 group （P 〈 0.05）, the NR2B expression reduced （P 〈 0.05）. Conclusion Subanesthetic doses of ketamine may reverse.partially hyperalgesia and down regulate the high expression of NR2B in hippocampus of NP model.