中文摘要：

目的：探讨大麻素受体1（CBR1）对神经病理性疼痛（NP）大鼠空间学习记忆和内侧前额叶（ mPFC）脑区N-甲基-D-天冬氨酸（ NMDA）受体NR1亚基表达的影响。方法选择健康的Wistar雄性大鼠36只，按照随机数字表法随机分成4组（每组9只）：假手术组（ SO组）、神经病理性疼痛模型组（ NP组）、生理盐水组（ NS组）和CBR1拮抗剂组（ AM251组）。其中，NS组、AM251组是在NP模型的基础上分别在mPFC脑区注射等体积生理盐水和AM251。采用单侧坐骨神经干慢性压迫法制备NP模型。 SO组和NP组分别于术后第3、7、14、21和28天测量机械缩足阈和热缩足潜伏期。术后第29天，按照随机数字表法随机抽取18只NP模型利用立体脑定位仪将生理盐水、AM251分别注射到mPFC脑区。术后第30～37天进行八臂迷宫实验。行为学完成后立即处死大鼠，通过Western印迹法、RT-PCR及免疫荧光方法测定mPFC脑区CBR1、NR1亚基的mRNA 和蛋白表达水平以及磷酸化NR1亚基（ p-NR1-Ser896）的蛋白表达水平。结果与SO组比较，NP组的机械性缩足阈和热缩足潜伏期降低（均P＜0.05），空间学习记忆功能减退（P＜0.05）。与NS组比较，AM251组的空间学习记忆能力明显改善（P＜0.05）。与SO组（CBR1的mRNA和蛋白表达水平分别为：0.23±0.06，0.42±0.03）比较，NP组CBR1的mRNA（0.43±0.12）和蛋白表达水平（0.53±0.05）均增加（均P＜0.05）。与NS组（CBR1的mRNA和蛋白表达水平分别为：0.42±0.11，0.52±0.10）比较，AM251组CBR1的mRNA（0.53±0.05）和蛋白表达水平（0.98±0.17）均增加（均P＜0.05）。与SO 组（ NR1亚基的mRNA和蛋白表达水平及p-NR1亚基的蛋白表达水平分别为：1.50±0.15，0.65±0.05，0.79±0.15）比较，NP组NR1亚基的mRNA（0.94±0.07）和蛋白表达水平（0.24±0.05）均减少（均P＜0.05）， p-NR1亚基的蛋白表达水平（0.33±0.04）减少（P＜0.05）。与NS组（

英文摘要：

Objective To investigate the effect of cannabinoid receptor 1 （ CBR1 ） on spatial learning and memory function of neuropathic pain （ NP ） model rats and the expression of N-methyl-D-aspartic acid receptor 1（NR1） subunit in medial prefrontal cortex （mPFC）.Methods Thirty-six healthy male Wistar rats were randomly divided into 4 groups, with 9 rats in each group： the sham operated group （SO group）, the neuropathic pain model group （NP group）, the NP model group with an mPFC injection of saline （ NS group ） , and the NP model group with an mPFC injection of the CBR 1 antagonist AM251 （ AM251 group）.The NP model was prepared using the operation of chronic constriction injury （ CCI） of the right sciatic nerve.The mechanical withdrawal threshold （ MWT ） and the thermal withdrawal latency （TWL） of the rats in each group were detected at 3, 7, 14, 21 and 28 days after the operation.At 29 days after the operation , 18 rats of NP model were randomly selected and given an mPFC injection of saline or AM251 using a three-dimensional brain puncture.At days 30-37 after operation , the eight-arm maze test was performed to detect the spatial learning and memory function of the rats , and the rats were sacrificed immediately after this test.The expression levels of CBR1, NR1 and phosphorylated-N-methyl-D-aspartic acid receptor 1 （ p-NR1 ） （ Ser896 ） in the mPFC brain region were detected by Western blotting , RT-PCR and immunofluorescence.Results Compared with the SO group , the pain thresholds and the spatial learning and memory function of the rats in the NP group were significantly lower （ both P 〈0.05 ）.Compared with the NS group , the rats in the AM251 group showed improvement about spatial learning and memory function （ P〈0.05）.Compared with the SO group （ the mRNA and protein level of CBR 1：0.23 ± 0.06,0.42 ±0.03）, the mRNA（0.43 ±0.12） and protein （0.53 ±0.05） level of CBR1 in NP group increased （both P〈0.05）.Compared with the NS group