米索前列醇对APP/PS1转基因小鼠的神经保护作用  

Protective effect of misoprostol on neurodegeneration in APP/PS1 transgenic mice

作　　者：纪超男[1] 胡馨月[1] 郭远新[1] 齐云 魏玉玲[1] 阳群芳[1] 杨洋[1] 李昱[3] 杨俊卿[1] 

机构地区：[1]重庆医科大学药理学教研室、重庆市生物化学与分子药理学重点实验室,重庆400016 [2]西南药业股份有限公司,重庆400038 [3]重庆医科大学病理学教研室,重庆400016

出　　处：《中国药理学通报》2015年第3期334-339,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81070972)

摘　　要：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。Aim To investigate the protective effects of misoprostol on hippocampal and cortical neuronal injury in APP/ PS1 transgenic mice and its possible mechanism. Methods Mice were divided into 4 groups including youth group, elderly group, APP/PS1 group and misoprostol-treated group. Ten 24-month-old APP/ PS1 transgenic mice were randomized into two groups as APP / PS1 group and misoprostol-trearted group. Ten 24-month-old wild-type C57 mice were chosen as elderly group. Mice in misoprostol-treated group were administered with misoprostol （200μg · kg-l d- 1, P. o. ） five days a week for 20 weeks. Mice in the other two groups were administered with carboxy- methylcellulose sodium （200 μg · kg-1 d-1, p. o. ） five days a week for 20 weeks. Three days before miso- prostol treatment was stopped, ten 8-week-old wild- type C57 mice were chosen as youth group. The spatial learning and memory function was evaluated by Morris water maze. The hippocampal and cortical neuronal damage was detected by HE staining. SOD activities and MDA contents were measured by biochemistry method. The expression of Aβ in mice hippocampus and cortex was observed using the immunohistochemi-cal method. Results Compared with those of elderly group, the exploring time of mice was lengthened re- markably, the hippocampal and cortical neurons ap- peared obvious nucleus pycnosis and deep dye, the SOD activities were decreased significantly, the MDA contents and the levels of A[3 increased significantly in APP/PS1 group. Compared with those of APP/PS1 group, the exploring time of mice was shortened re- markably, the damage of hippocampal and cortical neurons reduced significantly, the SOD activities in- creased significantly, the MDA contents and the levels of Aβ decreased significantly in the misoprostol-treated group. Conclusion Our research results suggest that misoprostol has a significant neuroprotective effect on brain injury in APP/PS1 transgenie mice. The neuro- protective mechanism of misoprostol might be related to its antioxidativ

关 键 词：米索前列醇 APP/PS1 海马 皮层 AΒ EP 氧化应激 神经保护作用 

分 类 号：R332[医药卫生—人体生理学] R322.81[医药卫生—基础医学]