度洛西汀对抑郁模型大鼠海马S100B蛋白和信号通路ERK1/2-NF-κB表达的影响  

The effects of duloxetine on hippocampal S100B and signal pathway ERK1/2-NF-κB expression in depression rat

作　　者：杨坤[1] 于雪[1] 王敬兰[2] 胡义秋[3] 

机构地区：[1]天津市安定医院精神卫生研究所,天津300222 [2]天津市南开医院 [3]湖南农业大学科学技术师范学院心理学系

出　　处：《中华行为医学与脑科学杂志》2015年第5期397-401,共5页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目（30900484）;天津市卫生局重点课题（2010KR10）

摘　　要：目的 探讨度洛西汀对抑郁模型大鼠行为及海马S100B和信号通路ERK1/2-NF-κB表达的影响.方法 选取慢性轻度不可预知应激刺激法制备50只抑郁症模型大鼠,将其随机分为非干预组（B组,n=10）、不同用药时间的度洛西汀干预组C、D、E和F组,每组各10只.10只健康大鼠为对照组（A组）.各组灌胃：A组和B组（生理盐水28 d）,C组（生理盐水27d＋度洛西汀1 d）、D组（生理盐水21d＋度洛西汀7d）、E组（生理盐水14d＋度洛西汀14 d）和F组（度洛西汀28 d）].灌胃结束,应用旷场试验、糖水偏爱试验检测大鼠行为改变;Western blot检测各组海马S100B、ERK1/2及NF-κB的表达.结果 E和F组大鼠干预28 d后旷场试验水平得分、垂直运动得分与潜伏期分别为（69.68±14.61）分和（70.66±11.53）分,（20.94±10.92）分和（20.32±8.85）分,（1.1±0.4）s和（1.0±0.4）s,与A组（71.19±12.08）分、（20.42±8.76）分、（1.0±0.3）s比较,均差异无统计学意义（P＞0.05）;E、F组与其他两组比较,水平运动得分和垂直运动得分升高,潜伏期降低.最后一次应激结束后所进行的糖水偏爱实验显示A组糖水消耗率显著高于其他组,表明抑郁模型建立成功.灌胃28 d后B组糖水消耗率[（43±15）％]显著较A、E、F组[（63±11）％,（65±21）％,（67±6）％]减少（P＜0.05）.A、E、F组大鼠海马S100B、pERK1/2及pNF-κB表达显著高于B组（P＜0.05）.结论 度洛西汀能够改善抑郁模型大鼠的行为能力,2周以上起效,其机制可能通过S100B激活海马的信号通路ERK1/2-NF-κB发挥作用.Objective To analyze the effect of duloxetine on S100B and signal pathway ERK1/2-NF-κB expression in hippocampus in depression rat.Methods Chronic unpredictable mild stimulation was used to establish depressive model rats （n=50）.They were randomly divided into no-intervention group （n=10）,different treatment time of duloxetine group （C,D,E,F group,10 rats in each group）and then 10 normal rats were selected as control group.Behavior tests including open-field test and the saccharine preference test were used to test the behavioral change of rats after 28 days intragastric administration.Western blot was used to detect S100B,t-ERK1/2,pERK 1/2,t-NF-κB and pNF-κB expression in hippocampus.Results In open-field test,the crossing score,rearing score and latency of the rats in E,F group were （69.68± 14.61） and （70.66± 11.53） score,（20.94 ± 10.92） and （20.32±8.85） score,（1.1±0.4）s and（1.0±0.4） s respectively,and showed no significant difference with those of control group （（71.19±12.08） score,（20.42±8.76） score,（1.0±0.3）s） after 28 d intragastric administration （P＞0.05）,while the level score,vertical score were significantly higher than those in depressive model （P＜ 0.05）.In the saccharine preference test,the rats in E,F and control group exhibited increased saccharin preference compared with depressive model rats （P＜0.05）.The rats in E,F and control group exhibited increased S100B,pERK1/2 and pNF-κB expression in hippocampus compared with depressive model rats （P＜0.05）.Conclusion Duloxetine improves the behavioral ability of depression rat and exerts effect after 2 weeks.The ERK1/2-NF-κB signal pathway in hippocampus may participate in this mechanism.

关 键 词：度洛西汀 抑郁 S100B ERK1/2-NF-κB 

分 类 号：R749.4[医药卫生—神经病学与精神病学]