磷酸二酯酶-4抑制剂Ro20-1724对氯胺酮麻醉后学习记忆及大鼠海马cAMP/PKA-CREB-BDNF信号通路的影响  

Effects of phosphodiesterase-4 inhibitor Ro 20-1724 on learning and memory function after ketamine anesthesia and cAMP/PKA-CREB-BDNF signal pathway in immature rats

作　　者：彭生[1] 杨建平[1] 张晓庆[2] 刘功俭[3] 

机构地区：[1]苏州大学附属第一医院麻醉科,苏州215006 [2]同济大学附属同济医院麻醉科 [3]徐州医学院麻醉学院

出　　处：《中华行为医学与脑科学杂志》2014年第6期528-530,共3页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然基金资助项目（81000469）;江苏省卫生厅资助课题（H201070）

摘　　要：目的 观察磷酸二酯酶-4（PDE-4）抑制剂Ro 20-1724对氯胺酮导致幼年大鼠学习记忆障碍及海马cAMP/PKA-CREB-BDNF信号通路蛋白表达的影响.方法 21日龄SD大鼠24只,随机分为4组（n=6）,空白对照组（C组）,注射生理盐水2 ml,30 min后再注射生理盐水2 ml;氯胺酮组（K组）：腹腔注射氯胺酮70 mg·kg^-1,30min后腹腔注射生理眼盐水2ml;氯胺酮＋Ro 20-1724组（K＋Ro组）：腹腔注射氯胺酮70 mg·kg^-1,30 min后腹腔注射0.5 mg·kg^-1 Ro20-1724（2ml）;氯胺酮＋0.1％乙醇组（K＋E组）：腹腔注射氯胺酮70 mg· kg^-1,30 min后腹腔注射0.1％乙醇（Ro20-1724的溶媒）.所有大鼠每天给药1次,连续7d.第8～9天正常饲养.第10～13天采用Morris水迷宫连续4d定位航行实验,记录逃避潜伏期.第14天行空间探索实验,记录单位时间穿越平台次数.行为学测量结束,立即取海马.放射免疫法测量cAMP,Western bolt法测量PKA、p-CREB、BDNF含量.结果 相对于C组,K组逃避潜伏期显著增加,（P＜0.01）;穿越平台次数显著减少（P＜0.01）.相对于K组,K＋Ro组逃避潜伏期显著减少（P＜0.05,P＜0.01.）,穿越平台次数显著增加（P＜0.01）.相对于C组,K组大鼠海马CA1区cAMP、PKA、p-CREB、BDNF含量[（280±31）pmol/mg vs （210±19）pmol/mg,P＜0.01];1.32±0.11 vs 1.13±0.12,P＜0.01;2.61±0.22 vs 2.03±0.19,P＜0.01;1.51±0.14 vs 1.16±0.10,P＜0.05）显著下降.相对于K组,K＋Ro组cAMP、PKA、p-CREB、BDNF含量[（210±19）pmol/mg vs （240±27）pmol/mg,P＜0.05];1.13±0.12 vs 1.28±0.12,P＜0.05;2.03±0.19 vs 2.32±0.21,2.32±0.21;1.16±0.10 vs 1.37±0.11,P＜0.01）.K＋Ro组与C组,及K＋E组与K相比较,差异无统计学意义（P＞0.05）.结论 腹腔注射Ro 20-1724 0.5mg/kg可显著改善反复氯胺酮麻醉导致的幼年大鼠学习记忆障碍,cAMP/PKA-CREB-BDNF信号通路的激活参与了Ro 20-1724此作用.Objective To observe a new phosphodiesterase-4 inhibitor Ro 20-1724 on ketamine anesthesia-induced learning and memory impairment and cAMP/PKA-CREB-BDNF signal pathway in immature rats.Methods Twenty-four 21 day-old SD rats were randomly divided into 4 groups （n=6 each）：control group （group C） ;ketamine group （group K） ;ketamine＋Ro 20-1724 group（group K＋Ro） and ketamine＋vehicle （0.1% ethanol） group （group K＋E）.Ketamine 70 mg/kg was injected intraperitoneally（IP） once a day for 7 consecutive days in groups K,K＋Ro,and K＋E.Ro 20-1724 0.5 mg/kg and equal volume of vehicle were injected IP at 30 min after IP ketamine each time respectively.Morris water maze was used to assess learning and memory ability after 2 days normal feeding,the escape latency and frequency of passing the platform were recorded.The animals were killed after water maze test and the cAMP,PKA,p-CREB,and BDNF protein expression in hippocampus were detected.Results Repetitive ketamine anesthesia significantly prolonged the escape latency （P〈0.01）,decreased the frequency of passing the platform（P〈0.01）,and down-regulated the expression of cAMP,PKA,p-CREB,and BDNF protein （（280±31） pmol/mg vs （210± 19） mol/mg,P〈0.01 ; 1.32±0.11 vs 1.13±0.12,P〈0.01 ; 2.61 ±0.22 vs 2.03 ± ±0.19,P〈0.01 ; 1.51 ±0.14 vs 1.16±0.10,P〈0.05） ; Compared with group K,Ro 20-172,significantly attenuated the escape latency time（P〈0.05,P〈0.01）and increased the frequency of passing the platform（P〈0.01）,and ameliorated the expression of cAMP,PKA,p-CREB,and BDNF protein （（210± 19） pmoL/mg vs （240± 27） pmol/mg,P 〈0.05;1.13±0.12 vs 1.28±0.12,P〈0.05;2.03±0.19 vs 2.32±0.21,2.32±0.21;1.16±0.10 vs 1.37±0.11,P〈0.01）.There was no difference between group K＋Ro and group C,and between group K＋E and group K（P〉0.05）.Conclusion ketamine anesthesia-induced learning and memory impairment can be improved by Ro 20-1724,and cAMP/PKA-CREB-BDNF signal pathway in hippocampus

关 键 词：Ro 20-1724 氯胺酮麻醉 幼年大鼠 认知功能 

分 类 号：R614[医药卫生—麻醉学]