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目的:探讨自主跑轮运动对阿尔茨海默病(AD)模型小鼠学习记忆能力和海马内肿瘤坏死因子-α(TNF-α)、白介素10(IL-10)、核转录因子κB(NF-κB)表达的影响。方法:将45只跑轮合格的3月龄雄性昆明小鼠随机分为二甲基亚砜(DMSO)对照组(n=15)和Aβ1-42寡聚体注射组(n=30),分别于侧脑室注射DMSO和Aβ1-42寡聚体,Aβ1-42寡聚体注射1周后两组小鼠进行Morris水迷宫实验,通过比较两组小鼠的逃避潜伏期和穿越平台次数,检测Aβ1-42寡聚体注射组与DMSO对照组小鼠的学习记忆能力,证实侧脑室注射Aβ1-42寡聚体能够有效模拟AD模型。之后将Aβ1-42寡聚体注射组小鼠随机分成AD运动组(n=15)和AD安静组(n=15),AD运动组进行为期6周的自主跑轮运动,AD安静组和DMSO对照组正常饲养6周,不运动。AD运动组跑轮结束后,3组小鼠采用Morris水迷宫实验,通过比较3组小鼠的逃避潜伏期和穿越平台次数,检测3组小鼠的学习记忆能力。运动后的3组小鼠均采用免疫荧光染色方法观察小鼠海马CA1区和CA3区TNF-α、IL-10、NF-κB阳性表达率变化。结果:(1)Morris水迷宫实验结果表明,侧脑室注射药物1周后,Aβ1-42寡聚体注射组小鼠的逃避潜伏期明显高于DMSO对照组(P<0.05),穿越平台所在区域的次数显著低于DMSO对照组(P<0.05);跑轮结束后,AD安静组小鼠的逃避潜伏期明显高于AD运动组和DMSO对照组(P<0.05),穿越平台所在区域的次数明显低于AD运动组和DMSO对照组(P<0.05)。(2)免疫荧光结果显示,NF-κB和促炎细胞因子TNF-α在海马CA1区和CA3区的表达趋势均一致,AD安静组的阳性表达率显著高于AD运动组和DMSO对照组(P<0.05),而IL-10的阳性表达率则显著低于AD运动组和DMSO对照组(P<0.05),各检测指标在AD运动组和DMSO对照组的阳性表达率无显著差异(P>0.05)。结论:(1)自主跑轮运动可有效改善AD模型小鼠的学习记忆能力;(2)自主跑轮运动一方面通过抑制NF-KB的过度活化减少促炎细胞因子TNF-α的表达,另一方面促进抗炎细胞因子IL-10的表达。
OBJECTIVE: To investigate the effects of spontaneous run-of-the-mill exercise on learning and memory and the levels of tumor necrosis factor-α (TNF-α), interleukin 10 (IL-10) and nuclear factor kappa B (NF) in hippocampus of Alzheimer’s disease -κB) expression. METHODS: Forty-five male Kunming mice of three-month-long run were randomly divided into dimethylsulfoxide (DMSO) control group (n = 15) and Aβ1-42 oligomer injection group Two groups of mice were injected with DMSO and Aβ1-42 oligomers into the lateral ventricle and Morris water maze test was performed one week after Aβ1-42 oligomer injection. By comparing the escape latency and the number of crossing platforms, the Aβ1- 42 oligomer injection group and DMSO control group mice learning and memory capabilities, confirmed that intracerebroventricular injection of Aβ1-42 oligomers can effectively simulate the AD model. The Aβ1-42 oligomer-injected mice were randomly divided into AD exercise group (n = 15) and AD quiet group (n = 15). AD exercise group The control group was normally housed for 6 weeks without exercise. AD exercise group after the end of the run, the three groups of mice Morris water maze test, by comparing the three groups of mice escape latency and through the platform frequency, test three groups of mice learning and memory ability. The 3 groups of mice after exercise were used to observe the expression of TNF-α, IL-10 and NF-κB in hippocampal CA1 and CA3 area by immunofluorescence staining. Results: (1) Morris water maze test results showed that the escape latency of Aβ1-42 oligomer injection group was significantly higher than that of DMSO control group (P <0.05) one week after intracerebroventricular injection of drug, (P <0.05). At the end of the run, the escape latency of AD quiet mice was significantly higher than that of AD rats and DMSO control rats (P <0.05), and the number of passing through the platform was significantly lower AD exercise group and DMSO control group (P <0.05). (2) The results of immunofluorescence showed that the expression of NF-κB and TNF-α in hippocampal CA1 and CA3 regions were consistent, and the positive expression rate of AD quiet group was significantly higher than that of AD exercise group and DMSO control group P <0.05), while the positive expression rate of IL-10 in AD exercise group and DMSO control group was significantly lower than that in AD exercise group and DMSO control group (P <0.05) > 0.05). Conclusion: (1) Autonomous runner exercise can effectively improve the learning and memory ability of AD model mice; (2) Autonomous runner exercise can reduce the expression of proinflammatory cytokine TNF-α by inhibiting the over-activation of NF-KB, on the other hand, On the one hand, it promotes the expression of the anti-inflammatory cytokine IL-10.