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| 术后认知功能障碍老年小鼠海马内NogoA-NgR1通路的变化 |
| Changes of hippocampal NogoA NgR1 signaling in aged mice with postoperative cognitive dysfunction |
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| DOI： |
| 中文关键词: 术后认知功能障碍 老年小鼠 海马 神经生长抑制因子A Nogo受体1 |
| 英文关键词: Postoperative cognitive dysfunction Aged mice Hippocampus NogoA Nogo receptor 1 |
| 基金项目:国家自然科学基金（81471105） |
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| 摘要点击次数: 2823 |
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| 中文摘要: |
| 目的 观察术后认知功能障碍老年小鼠海马内神经生长抑制因子NogoA及其受体NgR1表达的变化，并探讨其可能机制。方法 采用异氟醚麻醉+腹腔探查术建立POCD模型。老年雄性C57BL/6小鼠40只，随机分为四组:O2+Saline组(OS组)、O2+NEP1-40组(ON组)、异氟醚麻醉+腹腔探查术+Saline组(SS组)及异氟醚麻醉+腹腔探查术+NEP1-40组(SN组)，每组10只。麻醉前7 d行右侧脑室置管;麻醉前2 h至行为学测试前2 h每天侧脑室注射NEP1-40(20 μg/2 μl)或等容的无菌生理盐水，连续注射8 d。术后第5天行旷场实验，第6、7天分别行场景性和条件性恐惧实验训练和测试。行为学测试后2 h，取小鼠海马组织，采用Western blot法检测NogoA、NgR1、RhoA、ROCK2和GAP43含量变化;Golgi染色检测海马CA1区神经元树突棘数量改变。结果 与OS和ON组比较，SS组在场景性恐惧实验测试中僵直反应百分比明显降低，海马内NogoA、NgR1、RhoA和ROCK2含量明显升高，GAP43含量和总的、新生的和成熟的树突棘数量明显减少(P<0.05);与SS组比较，SN组在场景性恐惧实验测试中僵直反应百分比明显升高，海马内RhoA和ROCK2含量明显降低，GAP43含量和总的、新生的和成熟的树突棘数量明显增多(P<0.05)。结论 麻醉手术致老年小鼠认知功能损害与其海马内NogoA-NgR1通路过度激活有关。 |
| 英文摘要: |
| Objective To observe the changes of hippocampal NogoA-NgR1 signaling on postoperative cognitive function (POCD) in aged mice, and explore the potential underling mechanism. Methods Isoflurane anesthesia and laparotomy were applied to establish the POCD model. Forty aged male C57BL/6 mice were randomly divided into the following four groups (n=10): group O2+saline (group OS), group O2+NEP1-40 (group ON), group isoflurane anesthesia+laparotomy surgery+saline (group SS), and group isoflurane anesthesia+laparotomy surgery+NEP1-40 (group SN). Cannula placement was performed into lateral ventricle 7 days before the surgery. Animals were subjected to an administration of NEP1-40 (20 μg/2 μl) or isochoric saline via intracerebroventricular injection once daily for 8 consecutive days, injection was given from 2 h before isoflurane anesthesia to the last behavioral test. Open field test was performed at 5th d after operation. Contextual and cued fear conditioning training and testing were exhibited at 6th and 7th d after operation, respectively. The hippocampus was harvested 2 h after the behavioral test. Western blot was used to detect the expressions of NogoA, NgR1, RhoA, ROCK2 and GAP43. Golgi staining was applied to measure the changes of dendritic spines in hippocampal CA1 area. Results Compared with the groups OS and ON, the freezing time in the contextual fear conditioning test was significantly decreased, the contents of NogoA, NgR1, RhoA and ROCK2 were significantly increased, the content of GAP43 and the number of dendritic spine were significantly decreased in group SS (P<0.05). Compared with the group SS, the freezing time in the contextual fear conditioning test was significantly increased, the contents of RhoA and ROCK2 were significantly decreased, the content of GAP43 and the number of dendritic spine were significantly increased in group SN (P<0.05). Conclusion Over-activated of hippocampal NogoA-NgR1 signaling participated in the pathogenesis of POCD in aged mice. |
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