吗氯贝胺早期干预对创伤后应激障碍大鼠行为及前额皮质pCREB水平的影响  

The effect of Moc early intervention on the behavior and expression of pCREB in prefrontal cortex of PTSD rats

作　　者：肖冰[1] 韩芳[1] 石玉秀[1] XIAO Bing, HAN Fang, SHI Yu-xiu(Department of Histology and Embryology, Basic Medical Sciences College, China Medical University, Shenyang 110122, Chin)

机构地区：[1]中国医科大学基础医学院组织学与胚胎学教研室,沈阳110122

出　　处：《解剖科学进展》2018年第2期184-187,共4页Progress of Anatomical Sciences

基　　金：国家自然科学基金(31140060);沈阳市科技项目(F16-205-1-35)

摘　　要：目的探讨吗氯贝胺(Moclobemide,Moc)早期干预对创伤后应激障碍(posttraumatic stress disorder,PTSD)模型大鼠行为及内侧前额皮质pCREB水平的影响。方法采用单一连续刺激(single prolonged stress,SPS)建立大鼠PTSD模型。取成年健康雄性Wistar大鼠48只,随机分为N+sham组(正常对照组),SPS+sham组(SPS刺激后腹腔注射与抑制剂等体积的生理盐水),SPS+Moc组(SPS刺激后腹腔注射吗氯贝胺),N+Moc组(正常大鼠腹腔注射吗氯贝胺)。吗氯贝胺按8mg/kg腹腔注射给药,每日一次,连续14d。采用旷场试验和高架十字迷宫检测大鼠行为表现,并于行为学实验完成后处死大鼠,取前额内侧皮质,采用Western blot检测pCREB的表达水平。结果SPS引起大鼠进入中央区次数减少和总的运动距离缩短,给予Moc后大鼠进入中央区次数增多和总的运动距离增加。SPS引起大鼠进入开臂次数的百分比和开臂停留时间百分比均显著降低,给予Moc后大鼠进入开臂次数的百分比和开臂停留时间百分比明显升高。SPS引起大鼠内侧前额皮质pCREB的表达水平降低,Moc干预后pCREB的表达量增加。结论吗氯贝胺对PTSD大鼠行为改善的作用,可能是与上调前额内侧皮质pCREB水平相关。Objective To investigate the effect of moclobemide（Moc） on the behavior and level of pCREB in prefrontal cortex （ mPFC ） in rats with posttraumatic stress disorder（PTSD）. Methods The SPS-method was used to set up PTSD models. A total of 48 male Wistar rats were randomly divided into N＋sham group, SPS＋sham group, SPS＋Moc group and N＋Moc group. Open-field （OF） and elevated plus maze （EPM） tests were used to evaluate rats＇ behavior. Western blot was used to detect the expression of pCREB in mPFC. Results SPS induced significantly the decrease of total distance and percentage of ratio entry. Moc increased significently the total distance and percentage of ratio entry. SPS induced significantly the reduction of percentage of open-arm into the maze and percentage of the open arm pause. Moc increased the percentage of the open-arm into the maze and percentage of the open arm pause. SPS induced the decreased level of pCREB- protein in mPFC, and the expression level of pCREB-protein in mPFC was upregulated after administration of Moc. Conclusion The improvement of moclobemide early intervention on anxiety-like behavior in PTSD rats might be related to the upregulation of pCREB-protein level in mPFC.

关 键 词：创伤后应激障碍 行为学 吗氯贝胺 内侧前额皮质 大鼠 

分 类 号：R749.4[医药卫生—神经病学与精神病学]