舍曲林抗创伤后应激障碍效应及其对一氧化氮的影响  

Anti-post-traumatic stress disorder effect of sertraline and its effect on nitric oxide

作　　者：孙树峥 张黎明[3] 姬雅君 李雷[3] 蒋湘云[3] 王恒林[2] 张有志[3] 

机构地区：[1]河北北方学院研究生部,河北张家口075000 [2]北京解放军第309医院麻醉科,北京100091 [3]军事医学科学院毒物药物研究所,北京100850 [4]沧州市中心医院麻醉科,河北沧州061000

出　　处：《中国药理学与毒理学杂志》2016年第4期317-322,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81001653);国家自然科学基金(30973516)~~

摘　　要：目的利用大鼠条件性恐惧模型,探讨舍曲林抗创伤后应激障碍(PTSD)作用与一氧化氮(NO)之间的关系。方法采用声音线索配对足底电击对成年雄性SD大鼠造成条件性恐惧应激,第2天进行消退训练。每天实验前1 h,ig给予舍曲林15 mg·kg-1,连续8 d。消退训练后第1,4和7天,分别测试大鼠僵住行为。第7天测试完成后取杏仁核,Griess法检测NO含量,Western蛋白印迹法检测神经型一氧化氮合酶(n NOS)与诱导型一氧化氮合酶(i NOS)表达水平。结果行为学结果显示,与正常对照组相比,消退对照组和消退训练组僵住不动时间均显著增高(P<0.01),提示大鼠条件恐惧造模成功。大鼠恐惧消退训练后第1和4天,舍曲林15 mg·kg-1组僵住不动时间均低于消退训练组(P<0.05);在第7天,显著低于消退训练组(P<0.01),提示舍曲林减轻了恐惧反应。舍曲林15 mg·kg-1组大鼠杏仁核区NO含量、n NOS和i NOS表达水平明显低于消退训练组(P<0.01)。结论舍曲林能促进条件恐惧记忆的消退,在条件恐惧模型上具有抗PTSD效应,其作用机制可能与抑制NO过度释放有关。OBJECTIVE To investigate the relationship between the anti- post- traumatic stress disorder（PTSD）effect of sertraline and nitric oxide in fear conditioning rats. METHODS Conditioned fear stress was established by electric shock with a cue tone,and fear extinction training was carried out by giving the rats only tone signals the next day. The rats were treated with sertraline（15 mg·kg-1）intragastrically within 1 h before the experiment for 8 d. Freezing time was tested at the 1st,4th and7 th day after the extinction training in rats. The NO contents were detected by Griess method and the n NOS and i NOS level on amygdala was detected by Western blotting. RESULTS The behavior tests showed that compared with normal control group,the freezing time was significantly increased in extinction control group and extinction training group（P〈0.01）,indicating that the conditioned fear model of rats was successfully established. At the 1st and 4th day after conditioned fear extinction training in the rats,freezing time in sertraline（15 mg·kg-1）group was decreased compared with extinction training group（P〈0.05）. At the 7th day,the freezing time was significantly decreased（P〈0.01）,indicating that sertraline reversed the fear response. At the same time,the contents of NO,n NOS and i NOS on amygdala of rats in sertraline group were lower than that in extinction training group（P〈0.01）. CONCLUSION Sertraline can promote extinction of conditioned fear memory,suggesting that sertraline has antiPTSD effects on the model of fear condition in rats. The underlying mechanisms may be connected with NO.

关 键 词：舍曲林 创伤后应激障碍 一氧化氮合酶 条件性恐惧 杏仁核 

分 类 号：R965[医药卫生—药理学]