【摘要】 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(amyloidβprotein,Aβ)、糖原合成激酶-3β(glycogen synthase kinase-3β,GSK-3β)及雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)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m TOR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、m TOR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m TOR的表达变化有关。更多还原

【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 C57 BL /6J mice. Methods 36 male C57 BL /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 respectively for 7 consecutive days. On the 8thday,mice were tested in the Morris water maze,in which the latency to the platform and the proportion 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( m TOR). Results Compared 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 proportion 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 Aβ and 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 m TOR 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 vs1. 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-3β and m TOR in hippocampus.更多还原