硫化氢对创伤后应激障碍大鼠空间学习记忆能力及海马神经元放电的影响  

Effect of H_2S system on space learning and memory ability in PTSD model rat and on the frequency of spontaneous discharges of hippocampus neurons

作　　者：刘红霞[1] 于腊梅[1] 黄瑾[2] 张立霞[3] 岳真[4] 李庆忠[5] 

机构地区：[1]滨州医学院基础医学院生理学教研室,山东烟台264003 [2]滨州医学院附属医院院办,山东烟台264003 [3]滨州医学院医药研究中心,山东烟台264003 [4]滨州医学院基础医学院生物化学教研室,山东烟台264003 [5]滨州医学院药理学教研室,山东烟台264003

出　　处：《中国药理学通报》2017年第2期206-211,共6页Chinese Pharmacological Bulletin

基　　金：山东省自然科学基金资助项目(NoZR2013HL009;ZR2013HL002;ZR2013HL003;ZR2013HL007);烟台市科技发展计划项目(No2012ZH248);山东省高校科技计划项目(NoJ12LM03)

摘　　要：目的探讨创伤后应激障碍(posttraumatic stress disorder,PTSD)大鼠行为学改变及脑内胱硫醚-β-合成酶(cysta-thionine-β-synthase,CBS)/硫化氢(hydrogen sulfide,H_2S)水平的变化,并研究外源性补充H_2S对大鼠行为学影响的作用及机制。方法应用连续单一应激方案制备创伤后应激障碍动物模型,用Morris水迷宫检测大鼠空间学习记忆能力,Western blot技术和亚甲基蓝法检测海马脑区CBS/H_2S体系含量,用多管微电极在体细胞外电生理记录海马神经元放电情况。结果 (1)与正常对照组比较,PTSD组大鼠逃避潜伏期增加(P<0.01),在平台所在象限停留时间百分比和通过原平台位置次数明显减少(P<0.01);海马脑区的CBS/H_2S体系含量明显降低(P<0.01,P<0.05)。(2)与PTSD组比较,PTSD+硫氢化钠(sodium hydrosulfide,NaH S)组大鼠逃避潜伏期减小(P<0.01),在平台所在象限停留时间百分比和通过原平台位置次数明显增加(P<0.01)。(3)微量压力注射L-半胱氨酸(L-cysteine)使海马神经元自发放电频率明显升高(P﹤0.01)。结论PTSD大鼠通过抑制海马脑区CBS/H_2S体系导致空间学习记忆能力降低。H_2S改善PTSD大鼠空间学习记忆能力的机制可能与其增加海马神经元放电频率和兴奋性有关。海马脑区CBS/H_2S体系导致空间学习记忆能力降低。H_2S改善PTSD大鼠空间学习记忆能力的机制可能与其增加海马神经元放电频率和兴奋性有关。Aim To explore the behavior and CBS /H2 S levels of hippocampus in post traumatic stress dis-order （PTSD）rats and study the effect of exogenous H2 S on PTSD rats.Methods Single prolonged stress paradigm was adopted to prepare PTSD animal model. Morris water maze test was adopted to test space learn-ing and memory ability.CBS /H2 S content in hippo-campus tissue sample was measured using Western blot and methylene blue method.In vivo extracellular single unit recording was used to examine the frequency of spontaneous discharges of hippocampus neurons.Re-sults ① Escape latency increased and quadrant time （%）and platform crossing times decreased in Morris water maze test of PTSD group compared with normal group（P 〈0.01 ）.CBS /H2 S level in hippocampus tis-sue of PTSD group also decreased compared with nor-mal group （P 〈0.01 ,P 〈0.05 ）.② Escape latency decreased and quadrant time（%）and platform cross-ing times increased in Morris water maze test of NaHS＋PTSD group compared with PTSD group（P 〈0.01 ）.③ L-cysteine increased the frequency of spontaneous discharges of hippocampus neurons（P 〈 0.01 ）.Con-clusions Learning and memory ability decrease in PTSD model rats owing to the inhibition of CBS /H2 S content in hippocampus tissue.The mechanism of be-havior improvement of H2 S on PTSD model rat is possi-bly related to the excitation of H2 S on frequency of spontaneous discharges of hippocampus neurons.

关 键 词：硫化氢 胱硫醚-Β-合成酶 硫氢化钠 创伤后应激障碍 海马 在体细胞外电生理记录 

分 类 号：R-332[医药卫生] R322.81