中文摘要：

目的：研究神经病理性疼痛（neuropathic pain,NP）对大鼠空间学习记忆功能和内侧前额叶（medical prefrontal cortex,m PFC）钙/钙调素依赖性蛋白激酶Ⅱ（alpha calcium/calmodulindependent protein kinaseⅡ,Ca MKⅡ）磷酸化水平以及突触后密度蛋白95（postsynaptic density protein 95,PSD95）表达的影响。方法：选择经过八臂迷宫训练的雄性健康Wistar大鼠32只,将大鼠随机分为4组,神经病理性疼痛模型组（NP group,NP组,n=8）,NP模型m PFC注射生理盐水组（NS组,n=8）,NP模型m PFC注射Ca MKⅡ抑制剂KN-93组（KN-93组,n=8）和假手术组（sham operated group,SO组,n=8）。采用坐骨神经慢性压迫损伤制备大鼠NP模型。各组大鼠分别于术后第7、14、21、28和35天测机械缩足阈（mechanical withdrawal threshold,MWT）和热缩足潜伏期（thermal withdrawal latency,TWL）,第29-35天再次进行八臂迷宫实验以检测大鼠的空间学习和记忆功能。术后第33天采用立体脑穿刺进行药物干预试验,建立NP模型m PFC注射生理盐水组（NS组）和NP模型m PFC注射Ca MKⅡ抑制剂KN-93组（KN-93组）两组实验模型,第35天进行八臂迷宫检测大鼠的空间学习和记忆功能,检测后立即处死大鼠,通过Western Blotting、RT-PCR和免疫荧光方法测定m PFC部位Ca MKⅡ磷酸化位点Thr305磷酸化水平和突触小体内PSD95表达水平。结果：与SO组相比,NP组、NS组和KN-93组的术后痛阈明显降低（P〈0.05）。与SO组相比,NP组空间学习和记忆功能减退,PSD95表达升高,Ca MKⅡ-Thr305水平升高（P〈0.05）。与NS组比较,KN-93组空间学习和记忆功能改善,PSD95表达降低,Ca MKⅡ-Thr305水平降低（P〈0.05）。结论：NP能引起大鼠空间学习和记忆能力减退并使m PFC脑区的PSD95表达水平和Ca MKⅡ磷酸化水平升高。

英文摘要：

Objective： To evaluate the effects of neuropathic pain on spatial learning and memory and the expression of Ca MK Ⅱ phosphorylation and postsynaptic density protein 95（PSD95） in medial prefrontal cortex（m PFC） of the rats. Methods： Male Wistar rats（n = 32） previously trained in eight-arm maze were randomly divided into 4 groups： neuropathic pain group（NP group, n = 8）, m PFC of NP model injected with saline group（NS group, n = 8）, m PFC of NP model injected with KN-93 group（KN-93 group, n = 8）, and sham operated group（SO group, n = 8）. The NP model was produced by chronic constriction injury of the sciatic nerve. Mechanical withdrawal threshold（MWT） and thermal withdrawal latency（TWL） were measured on 7th, 14 th, 21 st and 28 th days after operation. During the 29 th - 35 th days after operation, eightarm maze was used to examine the spatial learning and memory. Drug intervention trial was conducted by injecting saline or KN-93 into m PFC of NP model using stereotaxic apparatus to establish the NS group and the KN-93 group on the 33 rd day, and examine the spatial learning and memory on the 35 th day. After the test, rats were sacrificed for measuring expression of PSD95 and Ca MK Ⅱ Phosphorylation sites Thr305 in m PFC by Western Blotting, RT-PCR and Immunofluorescence methods. Results： Compared with SO group, the thresholds of MWT and TWL in NP group, NS group and KN-93 group were significantly decreased（P 0.05） and the ability of spatial learning and memory in NP group was declined, while the expression of PSD95 and Ca MK Ⅱ- Thr305 was increased（P 0.05）. Compared with NS group, the ability of spatial learning and memory in KN-93 group was improved（P 0.05）, while the expression of PSD95 and Ca MK Ⅱ- Thr305 was reduced（P 0.05）. Conclusion： Under condition of experimental neuropathic pain, spatial memory can be impaired accompanied with up-regulation of PSD95 and Ca MK Ⅱ-Thr305 in medial prefrontal cortex in rats.