CAJ | 학술논문

目的：认知功能障碍的发病机制尚不明确。探讨美金刚对脂多糖所致C57BL／6J小鼠空间学习记忆能力的影响。方法36只C57BL／6J小鼠随机列表法分为对照组、脂多糖组、美金刚组，每组12只。3组分别连续7 d腹腔注射等容量等渗盐水，脂多糖和美金刚混合溶液。于第8天进行Morris水迷宫实验，记录登台潜伏期及平均靶象限活动时间。取海马组织测定淀粉样蛋白β（amyloid βprotein， Aβ）、糖原合成激酶-3β（glycogen synthase kinase-3β， GSK-3β）及雷帕霉素靶蛋白（mammalian tar-get of rapamycin， mTOR）的含量。结果脂多糖组较对照组登台潜伏期显著延长[（71．01±13．21）s vs （50．56±9．89）s， P＜0．05]、平均靶象限活动时间显著缩短[（42．58±7．85） s vs （63．74±12．43） s， P＜0．05]、海马Aβ及GSK-3β表达显著增加[（1．75±0．43） vs （1．27±0．23），（184．0±18．6）％ vs （100．0±12．1）％， P＜0．05]，但mTOR明显下降[（75．0±13．5）％ vs （100．0±10．3）％， P＜0．05]；美金刚组较脂多糖组登台潜伏期显著缩短[（61．45±7．65）s vs （71．01±13．21）s， P＜0．05]、平均靶象限活动时间显著延长[（58．25±9．02）s vs （42．58±7．85）s， P＜0．05]、海马Aβ及GSK-3β、mTOR明显下调[（1．35±0．28） vs （1．75±0．43），（92．4±10．8）％vs （184．0±18．6）％，（97．0±14．3）％vs （75．0±13．5）％， P＜0．05]。结论美金刚可改善脂多糖所致小鼠空间学习记忆能力下降，可能与海马组织中GSK-3β及mTOR的表达变化有关。
목적：인지공능장애적발병궤제상불명학。탐토미금강대지다당소치C57BL／6J소서공간학습기억능력적영향。방법36지C57BL／6J소서수궤렬표법분위대조조、지다당조、미금강조，매조12지。3조분별련속7 d복강주사등용량등삼염수，지다당화미금강혼합용액。우제8천진행Morris수미궁실험，기록등태잠복기급평균파상한활동시간。취해마조직측정정분양단백β（amyloid βprotein， Aβ）、당원합성격매-3β（glycogen synthase kinase-3β， GSK-3β）급뢰파매소파단백（mammalian tar-get of rapamycin， mTOR）적함량。결과지다당조교대조조등태잠복기현저연장[（71．01±13．21）s vs （50．56±9．89）s， P＜0．05]、평균파상한활동시간현저축단[（42．58±7．85） s vs （63．74±12．43） s， P＜0．05]、해마Aβ급GSK-3β표체현저증가[（1．75±0．43） vs （1．27±0．23），（184．0±18．6）％ vs （100．0±12．1）％， P＜0．05]，단mTOR명현하강[（75．0±13．5）％ vs （100．0±10．3）％， P＜0．05]；미금강조교지다당조등태잠복기현저축단[（61．45±7．65）s vs （71．01±13．21）s， P＜0．05]、평균파상한활동시간현저연장[（58．25±9．02）s vs （42．58±7．85）s， P＜0．05]、해마Aβ급GSK-3β、mTOR명현하조[（1．35±0．28） vs （1．75±0．43），（92．4±10．8）％vs （184．0±18．6）％，（97．0±14．3）％vs （75．0±13．5）％， P＜0．05]。결론미금강가개선지다당소치소서공간학습기억능력하강，가능여해마조직중GSK-3β급mTOR적표체변화유관。
[Abstract ] Objective The pathogenesis underlying cognitive dysfunction has yet to be fully elucidated.The article was to investigate the effects of memantine on lipopolysaccharide (LPS)-induced spatial learning and memory impairment in C57BL/6J mice. Methods 36 male C57BL/6J mice were randomly divided into 3 groups:control group (C group), lipopolysaccharide group (L group) and memantine group (M group) (n=12).Mice in C, L and M groups were intraperitoneally injected with the same volume of saline, LPS and LPS plus memantine re-spectively for 7 consecutive days.On the 8th day, mice were tested in the Morris water maze, in which the latency to the platform and the propor-tion of time spent in the target quadrant were recorded .Then the mice were sacrificed and the hippocampi were harvested for the determination of expression levels of Amyloid-β(Aβ), glycogen synthase kinase-3β(GSK-3β) and mammalian target of rapamycin (mTOR). Results Com-pared with C group, L group significantly prolongated the latency to the platform (71.01 ±13.21 vs 50.56 ±9.89, P<0.05), decreased the propor-tion of time spent in the target quadrant (42.58 ±7.85 vs 63.74 ±12.43, P<0.05) and increased the levels of hippocampal Aβand GSK-3β(1.75 ±0.43 vs 1.27 ±0.23, 184.0 ±18.6 vs 100.0 ±12.1, P<0.05), (75.0 ±13.5 vs 100.0 ±10.3, P<0.05), while mTOR levels decreased significantly (97.0 ±14.3 vs 75.0 ±13.5, P<0.05).Compared with L group, M group significantly prolongated the latency to the platform (61.45 ±7.65 vs 71.01 ±13.21, P<0.05), decreased the proportion of time spent in the target quadrant shortened (58.25 ±9.02 vs 42.58 ±7.85, P<0.05) and increased the expression of hippocampal Aβ(1.35 ±0.28 vs 1.75 ±0.43,92.4 ±10.8 vs 184.0 ±18.6, P <0.05). Conclusion Memantine contributes to the improvement of LPS-induced spatial learning and memory impairment, which is probably related to the changes of the expression of GSK-3βand mTOR in hippocampus.