阿司匹林通过促进海马功能性神经再生改善颞叶癫痫慢性期小鼠的空间记忆能力
发布时间：2018-10-26 17:20
【摘要】：目的评估阿司匹林(aspirin)通过抑制脑内炎症反应对颞叶癫痫(TLE)慢性期小鼠空间学习记忆能力的影响,并从海马神经再生角度初探其机制。方法匹鲁卡品(pilocarpine)制作小鼠TLE模型,在慢性期分别腹腔注射不同剂量阿司匹林(20、60、80mg/kg)或同体积生理盐水,用Western blot和ELISA检测海马环氧化物酶-2(COX-2)和前列腺素E2(PGE2)变化,Morris水迷宫实验评估动物的空间学习记忆能力并观察海马神经元C-fos表达变化,BrdU+C-fos免疫荧光双标染色观察齿状回新生细胞的功能整合。重复测量(repeated measures)ANOVA比较各组水迷宫潜伏期,One-way ANOVA方法分析各组染色阳性细胞计数结果。结果腹腔注射60、80mg/kg阿司匹林可以明显降低海马COX-2和PGE2的表达(P0.01)。与正常同龄对照组比较,TLE慢性期动物在Morris水迷宫任务中的表现明显下降,而与生理盐水注射模型组比较,阿司匹林治疗组明显缩短了定位航行实验第3~5天的潜伏期并提高了空间探索实验中穿越目的象限的时间比例(P0.01)。BrdU+C-fos免疫荧光染色结果显示阿司匹林组动物齿状回双标细胞数量较生理盐水注射组明显增多(P0.01)。结论阿司匹林可以改善TLE慢性期小鼠空间记忆能力。通过抑制脑内炎症反应、改善齿状回微环境,促进海马功能性神经再生可能是阿司匹林的治疗作用机制之一。
[Abstract]:Objective to evaluate the effect of aspirin (aspirin) on spatial learning and memory in (TLE) mice with temporal lobe epilepsy by inhibiting inflammatory response in the brain, and to explore its mechanism from the perspective of hippocampal nerve regeneration. Methods the TLE model of mice was induced by pilocarpine (pilocarpine). At the chronic stage, different doses of aspirin (2060 mg / kg) or saline of the same volume were injected intraperitoneally. Western blot and ELISA were used to detect the changes of COX-2 and PGE2 in hippocampus. Morris water maze test was used to evaluate the ability of spatial learning and memory and to observe the expression of C-fos in hippocampal neurons. The functional integration of nascent cells in dentate gyrus was observed by BrdU C-fos double immunofluorescence staining. The latency of water labyrinth in each group was compared by repeated measurement of (repeated measures) ANOVA, and the count of positive cells in each group was analyzed by One-way ANOVA method. Results the expression of COX-2 and PGE2 in hippocampus was significantly decreased by intraperitoneal injection of aspirin (60 mg / kg) (P0.01). Compared with the normal control group, the performance of Morris water labyrinth was significantly decreased in the chronic phase of TLE, while that in the saline injection model group was significantly lower than that in the normal saline injection group. Aspirin treatment group significantly shortened the latency of the 3rd day of the navigation experiment and increased the proportion of time passing through the target quadrant in the space exploration experiment (P0.01). BrdU C-fos immunofluorescence staining results showed that aspirin was used in the experiment. The number of double labeled cells in dentate gyrus in forest group was significantly higher than that in saline injection group (P0.01). Conclusion Aspirin can improve the spatial memory ability of chronic TLE mice. Inhibiting inflammation in brain, improving microenvironment of dentate gyrus and promoting functional nerve regeneration in hippocampus may be one of the therapeutic mechanisms of aspirin.
【作者单位】： 西安交通大学医学部基础医学院神经生物学研究所;西安交通大学医学部基础医学院人体解剖与组织胚胎学系;
【基金】：国家自然科学基金面上项目资助(No.81171232,81371427)~~
【分类号】：R965
本文编号：2296438
[Abstract]:Objective to evaluate the effect of aspirin (aspirin) on spatial learning and memory in (TLE) mice with temporal lobe epilepsy by inhibiting inflammatory response in the brain, and to explore its mechanism from the perspective of hippocampal nerve regeneration. Methods the TLE model of mice was induced by pilocarpine (pilocarpine). At the chronic stage, different doses of aspirin (2060 mg / kg) or saline of the same volume were injected intraperitoneally. Western blot and ELISA were used to detect the changes of COX-2 and PGE2 in hippocampus. Morris water maze test was used to evaluate the ability of spatial learning and memory and to observe the expression of C-fos in hippocampal neurons. The functional integration of nascent cells in dentate gyrus was observed by BrdU C-fos double immunofluorescence staining. The latency of water labyrinth in each group was compared by repeated measurement of (repeated measures) ANOVA, and the count of positive cells in each group was analyzed by One-way ANOVA method. Results the expression of COX-2 and PGE2 in hippocampus was significantly decreased by intraperitoneal injection of aspirin (60 mg / kg) (P0.01). Compared with the normal control group, the performance of Morris water labyrinth was significantly decreased in the chronic phase of TLE, while that in the saline injection model group was significantly lower than that in the normal saline injection group. Aspirin treatment group significantly shortened the latency of the 3rd day of the navigation experiment and increased the proportion of time passing through the target quadrant in the space exploration experiment (P0.01). BrdU C-fos immunofluorescence staining results showed that aspirin was used in the experiment. The number of double labeled cells in dentate gyrus in forest group was significantly higher than that in saline injection group (P0.01). Conclusion Aspirin can improve the spatial memory ability of chronic TLE mice. Inhibiting inflammation in brain, improving microenvironment of dentate gyrus and promoting functional nerve regeneration in hippocampus may be one of the therapeutic mechanisms of aspirin.
【作者单位】： 西安交通大学医学部基础医学院神经生物学研究所;西安交通大学医学部基础医学院人体解剖与组织胚胎学系;
【基金】：国家自然科学基金面上项目资助(No.81171232,81371427)~~
【分类号】：R965
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