摘要： 目的 探讨淫羊藿苷对创伤后应激障碍（PTSD）大鼠恐惧记忆的影响及作用机制。方法 选取雄性SD大鼠30只，应用单一连续应激（SPS）构建PTSD大鼠模型。将模型大鼠按随机数字表法分成SPS组、淫羊藿苷组及淫羊藿苷+K252a组，其中K252a为酪氨酸激酶受体B （TrkB）抑制剂，每组10只；另取10只正常大鼠作为对照组。淫羊藿苷组及淫羊藿苷+K252a组大鼠均于SPS造模1 d后灌胃给药淫羊藿苷，剂量为20 mg/kg，1次/d，共2周。对照组、SPS组给予等剂量生理盐水。K252a为造模7 d后侧脑室注射单次给药。2周后，旷场试验、高架十字迷宫实验、条件性恐惧测试检测各组大鼠焦虑、抑郁及恐惧记忆障碍状况；分子对接验证淫羊藿苷与脑源性神经营养因子（BDNF）的结合活性。免疫组化检测大鼠杏仁核BDNF和TrkB的表达； Western blotting检测BDNF和TrkB蛋白的相对表达。免疫荧光检测大鼠杏仁核突触后密度蛋白95 （PSD95）和突触素（SYN）的表达。结果 淫羊藿苷与BDNF具有较好的结合活性。与对照组相比，SPS组和淫羊藿苷+K252a组大鼠进入中心区域次数和中心区域运动距离百分比明显降低，开臂进入（OE）和开臂时间（OT）明显降低，僵住时间和排便次数明显增加，BDNF、TrkB、PSD95和SYN蛋白表达明显降低（P < 0.05）；而与SPS组相比，淫羊藿苷组大鼠进入中心区域次数和中心区域运动距离百分比明显增加，OE和OT明显增加，僵住时间和排便次数明显减少，BDNF、TrkB、PSD95和SYN蛋白表达明显增加（P < 0.05）。结论 淫羊藿苷可以有效缓解SPS诱导的大鼠恐惧记忆障碍，这种保护作用可能与激活BDNF/TrkB信号通路及上调突触相关蛋白SYN和PSD95有关。

淫羊藿苷调控BDNF/TrkB信号通路及突触可塑性对创伤后应激障碍大鼠恐惧记忆的改善作用

刘晓晨^1,2, 金娜³, 高源泽³, 史宝湘⁴, 单伟¹

1. 锦州医科大学基础医学院解剖学教研室, 辽宁 锦州 121001;
2. 盘锦市中心医院VIP病房2病区, 辽宁 盘锦 124010;
3. 锦州医科大学第三临床医学院, 辽宁 锦州 121001;
4. 锦州医科大学护理学院, 辽宁 锦州 121001

收稿日期:2023-04-03出版日期:2024-01-30发布日期:2024-01-09
通讯作者:单伟E-mail:604616912@qq.com
作者简介:刘晓晨(1987-),女,主治医师,硕士研究生.
基金资助:辽宁省教育厅科学研究经费项目（JYTJCZR2020087）；辽宁省大学生创新训练计划项目（S202210160013）


关键词: 淫羊藿苷, 创伤后应激障碍, 恐惧记忆, 脑源性神经营养因子, 突触可塑性
Abstract: Objective To investigate the effects and mechanisms of icariin on changes in fear memory in post-traumatic stress disorder (PTSD) rats. Methods Thirty male SD rats were used to construct a rat model of single prolonged stress (SPS). The model rats were randomly divided into the SPS, icariin, and icariin + K252a (tyrosine kinase receptor B inhibitor) groups (n=10 each; another 10 normal rats were used as the control group). The icariin and icariin + K252a groups were administered 20 mg/kg icariin by gavage once per day after SPS, while the control and SPS groups were administered the same dose of normal saline. K252a cells were injected into the lateral ventricles. After 2 weeks, anxiety, depression, and fear memory disorder in rats in each group were detected by the mine experiment, elevated cross maze experiment, and conditional fear test. The binding activity of icariin to brain-derived neurotrophic factor (BDNF) and the BDNF and TrkB expressions in the rat amygdala were detected by immunohistochemistry. The relative expressions of BDNF and TrkB proteins were detected by Western blotting. The expressions of postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) in the rat amygdala were detected using immunofluorescence. Results Icariin showed strong binding to BDNF. Compared with the control group, the times of entering the central area and the percentage of movement distance in the central area in the SPS group and the icariin+K252a group were significantly reduced. The open arm entry (OE) and arm opening time (OT) were significantly reduced, the freezing time and defecation times were significantly increased, and the expressions of the BDNF, TrkB, PSD95, and SYN proteins were significantly reduced (P < 0.05). Compared with the SPS group, the icariin group rats had significantly increased times of entering the central area and percentages of movement distance in the central area, significantly increased OE and OT, significantly reduced the time of immobilization and defecation, and significantly increased the expressions of BDNF, TrkB, PSD95, and SYN proteins (P < 0.05). Conclusion Icariin effectively alleviated the fear memory impairment induced by SPS in rats. This protective effect is related to BDNF/TrkB signaling pathway activation and upregulated PSD95 and SYN expression.
Key words: icariin, post traumatic stress disorder, fear memory, brain derived neurotrophic factor, synaptic plasticity
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