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| 氯胺酮下调神经连接蛋白-1在创伤后应激功能障碍动物模型中的作用 |
| Role of ketamine-mediated-decreased expression of neuroligin-1 in the hippocampus on rats with post-traumatic stress disorder |
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| DOI：10.12089/jca.2018.01.019 |
| 中文关键词: PTSD 氯胺酮 认知功能 神经连接蛋白-1 |
| 英文关键词: Post-traumatic stress disorder Ketamine Hippocampus Neuroligin-1 |
| 基金项目:国家自然科学基金（81471105）；东南大学-南京医科大学合作研究重点项目（2242017K3DN05） |
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| 中文摘要: |
| 目的 观察氯胺酮是否可改善创伤后应激功能障碍(post-traumatic stress disorder,PTSD)症状及可能涉及的机制。方法 成年雄性SD大鼠60只,6～8周龄,随机分为四组:对照+生理盐水组(CN组)、对照+氯胺酮组(CK组)、PTSD+生理盐水组(PN组)、PTSD+氯胺酮组(PK组),每组15只。采用幽闭+足底电击法(IFS)建立PTSD模型。建模30 min后腹腔注射氯胺酮2.5 mg/kg,连续注射14 d。在建模后第14天,每组取12只大鼠开始行条件性恐惧实验和水迷宫实验;另外3只取海马组织,采用Western blot法检测神经连接蛋白-1(neuroligin-1,NLGN-1)含量。结果 条件性恐惧实验中,PN组僵直反应时间占总时间百分比明显高于CN组和PK组(P<0.01)。水迷宫实验中,训练第2、3、4、5天PN组的逃避潜伏期明显长于CN组(P<0.05);训练第2、4、5天PK组的逃避潜伏期明显短于PN组(P<0.05)。PN组海马内NLGN-1含量明显高于CN组和PK组(P<0.05)。结论 PTSD模型大鼠出现明显的恐惧记忆增强及海马相关的空间学习障碍,可能与海马中NLGN-1含量明显增加有关,氯胺酮可能通过降低海马中NLGN-1表达而减弱PTSD大鼠的恐惧记忆及提高海马相关的空间学习能力。 |
| 英文摘要: |
| Objective To observe whether ketamine improves the symptoms of post-traumatic stress disorder (PTSD). Methods Sixty male SD rats were randomized into four groups: groups CN, CK, PN and PK, 15 in each. PTSD animal model was established by inescapable foot shock (IFS) procedure. In groups PK and CK, rats were treated with ketamine 2.5 mg/kg by intraperitoneal injection beginning at 30 min after the IFS procedure once a day for 14 days. Twelve rats were used for behavioral tests, and the others were sacrificed to collect hippocampus tissues for Western blot in each group 14 d after IFS procedure, respectively. The expression of neuroligin (NLGN)-1 was detected by Western blot. Results In the fear conditioning test, compared with group CN, the percent age of freezing time in total time in group PN was significantly increased (P<0.01). Compared with group PN, the percent age of freezing time in PK group was significantly decreased (P<0.01). In the water maze test, compared with group CN, the escape latency of group PN was significantly increased on day 2, 3, 4, 5 of training period (P<0.05). Compared with group PN, the escape latency of group PK was significantly decreased on day 2, 4, 5 of training period (P<0.05). There was no significant difference in the time spent in the target quadrant. The expression of NLGN-1 in the hippocampus was significantly increased in PN group compared with group CN (P<0.05); compared with group PN, the expression of NLGN-1 in the hippocampus was significantly decreased in PK group (P<0.05). Conclusion The study suggest that the fear memory is significantly, increased and the hippocampus-dependent spatial learning capacity is impaired in the PTSD model rats. And the increased expression of hippocampal NLGN-1 may be involved in the development of PTSD. Ketamine mediated down-regulation of NLGN-1 in the hippocampus might contribute to attenuating the fear memory and improving the hippocampus-dependent spatial learning in the PTSD model rats. |
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