不同程度嗅球切除对小鼠认知功能、内嗅皮质、海马体积及神经病理的影响

摘要/Abstract

摘要： 目的：探讨不同程度嗅球切除对小鼠认知功能、内嗅皮质、海马体积及神经病理的影响。方法：选取健康雄性昆明小鼠60只，按随机数字表法分为假手术组、不完全切除组、完全切除组，各20只。脑立体定位后，完全切除组在前囟前3.4 mm垂直插入刀片切断嗅束，不完全切除组在前囟前4 mm以同样方式切断嗅球。假手术组只开窗、不切除嗅球。在术后第6周末、第12周末，对三组分别进行行为学测试和T2WI脑扫描，之后取脑、制作标本，并检测内嗅皮质、海马匀浆液中可溶性淀粉样前体蛋白α(sAPPα)/β淀粉样蛋白42(Aβ42)含量及胆碱乙酰转移酶(ChAT)/乙酰胆碱酯酶(AchE)活性。结果：在第12周末，与假手术组比较，不完全切除组和完全切除组潜伏期(IP)、第1次穿越原平台位置的时间(EIP)延长、在目标象限活动的时间(TQT)缩短(P＜0.05)，嗅皮质、海马体积萎缩(P＜0.05)；不完全切除组和完全切除组sAPPα含量降低、Aβ42含量升高(P＜0.05)；不完全切除组和完全切除组ChAT降低、AchE升高(P＜0.05)。与不完全切除组比较，完全切除组IP、EIP延长、TQT缩短(P＜0.05)；内嗅皮质、海马体积萎缩(P＜0.05)；sAPPα降低、Aβ42升高(P＜0.05)；ChAT降低、AchE升高(P＜0.05)。在第6周末，上述各观察指标在三组间变化不明显(P＞0.05)。与第6周末比较，第12周末上述各观察指标，在假手术组变化差异无统计学意义(P＞0.05)，但不完全切除组和完全切除组均有变化(P＜0.05)。结论：不同程度嗅球切除可导致小鼠认知功能障碍、内嗅皮质、海马体积萎缩及神经病理变化，通过嗅球摘除可建立阿尔茨海默病动物模型。

关键词: font-size:medium, ">阿尔茨海默病；嗅球；学习记忆；内嗅皮质、海马体积

Abstract: Objective： To investigate the effects of olfactory bulb resection on cognitive function， volumes and neuropathology of entorhinal cortex and hippocampus in mice. Methods： 60 healthy male Kunming mice were randomly divided into the sham operation group (n=20)， incomplete resection group (n=20)， and complete resection group (n=20). After stereotactic localization of the brain， the olfactory tract was cut off by inserting the blade vertically 3.4 mm from the front of the anterior fontanelle in the complete resection group. The olfactory tract was cut off in the same way 4 mm from the front of the anterior fontanelle in the incomplete resection group. The window was opened and the olfactory bulb was not resected in the sham operation group. At the end of week 6 and week 12 after operation， the behavior test and T2WI brain scan were carried out in the three groups. Then the brain was taken out to make the specimens.The contents of soluble amyloid precursor protein α (sAPPα)/ β amyloid protein42(Aβ42) and the activity of choline acetyltransferase (ChAT)/acetylcholinesterase (AchE) in the entorhinal cortex and hippocampal homogenate were detected.Results： At the end of week 12， compared to the sham operation group， the incubation period (IP) and time of the first crossing of the original platform position (EIP) were obviously prolonged and time spent in the target quadrant (TQT) was obviously shortened (P<0.05) in the incomplete resection group and complete resection group. The volumes of the entorhinal cortex and hippocampus obviously atrophied in the incomplete resection group and the complete resection group (P<0.05). The content of sAPPα obviously decreased and the content of Aβ42 obviously increased in the incomplete resection group and the complete resection group (P<0.05). ChAT decreased obviously and AchE increased obviously in the incomplete resection group and the complete resection group (P<0.05). Compared with incomplete resection group， the IP and EIP were obviously prolonged and TQT was obviously shortened (P<0.05)； the volumes of the entorhinal cortex and hippocampus obviously atrophied (P<0.05)， the content of sAPPα obviously decreased and the content of Aβ42 obviously increased (P<0.05)； ChAT decreased obviously and AchE increased obviously (P<0.05) in the complete resection group. At the end of week 6， the above indexes did not change significantly among the three groups (P>0.05). Compared with that at the end of the 6th week， there were no statistically significant changes in the sham operation group at the end of the 12th week (P>0.05). However， there were changes in both incomplete resection group and the complete resection group (P<0.05). Conclusion： Varying degrees of olfactory bulb resection may lead to cognitive impairment， volume atrophy and neuropathological changes of entorhinal cortex and hippocampus in mice. Alzheimer′s disease animal model can be established by olfactory bulb removal.

Key words: font-size:medium, ">Alzheimer disease； Olfactory bulb； Learning and memory； Volumes of entorhinal cortex and hippocampus

中图分类号:

方侃, 胡怀明, 姜华军, 艾志兵, 周选民. 不同程度嗅球切除对小鼠认知功能、内嗅皮质、海马体积及神经病理的影响[J]. 中国医药导刊, 2021, 23(2): 128-132.

FANG Kan, HU Huaiming, JIANG Huajun, AI Zhibing, ZHOU Xuanmin. Effects of Olfactory Bulb Resection on Cognitive Function， Volumes and Neuropathology of Entorhinal Cortex and Hippocampus in Mice[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2021, 23(2): 128-132.

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