术后认知功能障碍老年小鼠海马内NogoA-NgR1通路的变化

发布时间：2018-03-07 07:52

本文选题：术后认知功能障碍　切入点：老年小鼠　出处：《临床麻醉学杂志》2017年05期 　论文类型：期刊论文

【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:O_2+Saline组(OS组)、O_2+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7d行右侧脑室置管;麻醉前2h至行为学测试前2h每天侧脑室注射NEP1-40(20μg/2μl)或等容的无菌生理盐水,连续注射8d。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2h,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(P0.05);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(P0.05)。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。
[Abstract]:Objective to observe the expression of nerve growth inhibitor (NogoA) and its receptor (NgR1) in hippocampus of senile mice with cognitive impairment after operation. Methods the POCD model was established by isoflurane anesthesia and abdominal cavity exploration. 40 old male C57BL / 6 mice were used. The rats were randomly divided into four groups: group O _ 2: O _ 2 Saline group: OS group (n = 10), NEP1-40 group (n = 10), Saline group (SS group) and NEP1-40 group (n = 10). Right ventricular catheterization was performed 7 days before anesthesia (n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 10, n = 7 days before anesthesia). Two hours before anesthesia and two hours before behavioral test, NEP1-40(20 渭 g / 2 渭 l or isovolumetric sterile saline was injected into the lateral ventricle every day for 8 days. The open field test was performed on the 5th day after operation. On the 6th and 7th day, the training and testing of scenario and conditioned fear were performed respectively. The hippocampal tissue of mice was taken at 2 hours after behavioral test. Western blot method was used to detect the changes of NgR1R1RhoAroCK2 and GAP43 content in hippocampal CA1 neurons. Results compared with OS and on groups, the percentage of stiffness in SS group was significantly lower than that in OS and on groups. The contents of NgR1 RhoA and ROCK2 in hippocampus increased significantly, and the total number of new and mature dendritic spine decreased significantly (P 0.05), and the percentage of stiffness in SNS group was significantly higher than that in SS group. The contents of RhoA and ROCK2 in hippocampus significantly decreased the content of GAP43 and the total number of new and mature dendritic spine increased significantly. Conclusion the cognitive impairment induced by anesthesia in aged mice is related to the excessive activation of NogoA-NgR1 pathway in hippocampus.
【作者单位】：南京大学医学院临床学院南京军区南京总医院麻醉科;东南大学附属中大医院麻醉科;
【基金】：国家自然科学基金(81471105)
【分类号】：R614

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