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目的观察米索前列醇对APP/PS1转基因小鼠海马和皮层损伤的保护作用并探讨其机制。方法实验动物设4组:转基因模型组和药物处理组APP/PS1转基因小鼠各10只,老年对照组为野生型C57小鼠10只,药物处理组给予米索前列醇,另两组给予羧甲基纤维素钠,均在小鼠24周龄时以200μg·kg-1的量开始灌胃给予,连续给药20周,每周连续5 d,每天1次;在指标测试阶段,另取10只8周龄野生型C57小鼠作为青年对照组。采用Morris水迷宫测试空间学习记忆能力,HE染色观察海马和皮层神经元形态变化,生化法检测海马和皮层SOD活性、MDA含量变化,免疫组织化学法检测海马和皮层Aβ表达情况。结果与老年对照组小鼠相比,转基因模型组小鼠寻台潜伏期明显延长,海马和皮层神经元出现明显核固缩,SOD活性明显下降,MDA含量明显增加,Aβ表达明显增多;给予米索前列醇后,APP/PS1转基因小鼠寻台潜伏期明显缩短,海马和皮层神经元核固缩明显减轻,SOD活性明显升高,MDA含量明显降低,Aβ表达明显减少。结论米索前列醇对APP/PS1转基因小鼠海马和皮层的神经损伤有显著保护作用,其机制可能与米索前列醇减轻APP/PS1转基因小鼠脑组织氧化应激有关。
Objective To observe the protective effect of misoprostol on the damage of hippocampus and cortex in APP / PS1 transgenic mice and to explore its mechanism. Methods The experimental animals were divided into 4 groups: 10 in the transgenic model group and APP / PS1 transgenic mice in the drug-treated group, 10 in the wild-aged control group, misoprostol in the drug-treated group, Sodium methylcellulose, were intragastrically administered at a dose of 200 μg · kg-1 at 24 weeks of age in mice and continuously administered for 20 weeks, once a week for 5 consecutive days. In the index test phase, Ten 8-week-old wild-type C57 mice served as a young control group. Morris water maze was used to test spatial learning and memory abilities. Morphological changes of hippocampal and cortical neurons were observed by HE staining. SOD activity and MDA content in hippocampus and cortex were detected by biochemical methods. Aβ expression in hippocampus and cortex was detected by immunohistochemistry. Results Compared with the aged control mice, the mice in the transgenic model showed a significantly longer incubation period, a significant nuclear pyknosis in the hippocampus and cortical neurons, a significant decrease in SOD activity, a significant increase in MDA content and a marked increase in Aβ expression in the transgenic mice; After PR, the latency of APP / PS1 transgenic mice was significantly shortened, the nuclear pyknosis of hippocampus and cortical neurons was significantly reduced, the activity of SOD was significantly increased, the content of MDA was significantly decreased and the expression of Aβ was significantly decreased. Conclusion Misoprostol has a significant protective effect on neuronal damage in hippocampus and cortex of APP / PS1 transgenic mice, which may be related to the reduction of oxidative stress induced by misoprostol in APP / PS1 transgenic mice brain.