中文摘要：

目的 评价钙/钙调素依赖性蛋白激酶Ⅱ（CaMKⅡ）在慢性痛致大鼠认知功能障碍中的作用.方法 实验Ⅰ 清洁级健康雄性SD大鼠24只,体重180～ 220 g,采用随机数字表法分为4组（n=6）：假手术组（S组）、假手术前注射m-AIP组（M-S组）、坐骨神经慢性压迫性损伤组（N-C组）和坐骨神经慢性压迫性损伤（CCI）术前注射m-AIP组（M-C组）.S组及M-S组仅暴露坐骨神经但不进行结扎,其余各组采用CCI法制备慢性痛模型.S组及M-S组分别于假手术前15 min鞘内注射生理盐水20 μl及m-AIP 20μl;N-C组及M-C组分别于CCI术前15 min鞘内注射生理盐水20μl及m-AIP 20μl.于术前及术后第4、7、10、14、17、21和28天时测定大鼠热缩足潜伏期（TWL）及机械缩足反应阈（MWT）,于术前及术后第7、14、21和28天时测定步入潜伏期时间（STL）.实验Ⅱ 清洁级健康雄性SD大鼠18只,体重180～ 220 g,采用随机数字表法分为3组（n=6）：假手术后注射m-AIP组（S-M组）、CCI术后对照组（C-N组）、CCI术后注射m-AIP组（C-M组）.S-M组假手术后7d鞘内注射m-AIP 20μl,C-N组及C-M组于CCI分别于术后7d鞘内注射生理盐水20 μl及m-AIP 20μl.于给药前及给药后2、4和8h时测定TWL、MWT和STL.结果 实验Ⅰ 与S组比较,N-C组术后各时点TWL缩短,MWT降低,术后第7、14和21天时STL缩短,M-C组术后各时点TWL缩短,MWT降低,术后第14和21天时STL缩短（P＜0.05）;与N-C组比较,M-C组术后第4、7和10天时MWT升高,第4和7天时TWL延长,第7天时STL延长（P＜0.05）.实验Ⅱ 与S-M组比较,C-N组给药后各时点TWL和STL缩短,MWT降低,C-M组给药后各时点STL缩短,给药后8h时TWL缩短,MWT降低（P＜0.05）,给药后2和4h时TWL和MWT差异无统计学意义（P＞0.05）.与C-N组比较,C-M组给药后2和4h时TWL延长,MWT升高（P＜0.05）,各时点STL差异无统计学意义（P＞0.05）.结论 CaMKⅡ参与了慢性痛致大鼠认知功能障碍的形成.

英文摘要：

Objective To evaluate the role of calcium/calmodulin-dependent protein kinase Ⅱ （CaMK Ⅱ） in cognitive dysfunction caused by chronic pain in rats.Methods The experiment was performed in 2 parts.In experiment Ⅰ,24 pathogen-free male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups （n =6 each） using a random number table：sham operation group （group S）,m-AIP injected before sham operation group （group M-S）,chronic sciatic nerve injury group （group N-C）,and m-AIP injected before chronic constriction injury （CCI） group （group M-C）.The sciatic nerve was only exposed but not ligated.Chronic pain was induced by CCI in N-C and M-C groups.The animals were anesthetized with intraperitoneal 1％ pentobarbital sodium.The sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.Normal saline 20 μ1 and m-AIP 20 μ/ were injected intrathecally at 15 min before sham operation in S and M-S groups,respectively,and at 15 min before CCI in N-C and M-C groups,respectively.The mechanical paw withdrawal threshold （MWT） and thermal paw withdrawal latency （TWL） were measured before CCI and on 4,7,10,14,17,21 and 28 days after CCI.Step-through latency （STL） was measured before CCI and on 7,14,21 and 28 days after CCI.In experiment Ⅱ,18 pathogen-free male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups （n =6 each） using a random number table：m-AIP injected after sham operation group （group C-N）,control after CCI group （group C-N） and m-AIP injected after CCI group （group C-M）.Group S-M received intrathecal injection of m-AIP 20 μl at 7 days after sham operation.Normal saline 20 μl and m-AIP 20 μ/ were injected intrathecally at 7 days after CCI in C-N and C-M groups,respectively.MWT,TWL and STL were measured before administration and at 2,4 and 8 h after administration.Results In experiment Ⅰ,compared with group S,MWT was significantly decreased at each time point after CCI,TWL was