摘要
目的研究葛根素对雌激素剥夺小鼠学习记忆和突触结构的影响。方法卵巢摘除(Ovx)或假手术(Sham)后一周,雌性小鼠给予4周的葛根素(Pur,40,120mg·kg-1,ip)或苯甲酸雌二醇(EB,4μg·d-1,sc)治疗。分别用Morri′s水迷宫和穿梭箱检测小鼠的空间记忆和主动回避行为;通过制备超薄切片电镜观测学习记忆相关脑区海马CA1和前皮层的突触超微结构变化。结果Ovx小鼠经120mg·kg-1 Pur治疗后,在水迷宫中搜寻平台的平均路径显著缩短(P<0.05),主动逃避电击的次数明显增多(P<0.01)。同时,葛根素增加Ovx小鼠海马和前皮层的突触后密度(PSD)厚度,并减小突触间隙宽度,但对突触界面曲度、突触活性带长度没有明显作用。结论长期Pur治疗可通过影响海马和前皮层突触结构改善雌激素剥夺小鼠的记忆损伤。
Abstract
OBJECTIVE To study the effects of puerarin (Pur) on learning-memory and synaptic structure in cerebral frontal cortex and hippocampus of estrogen-deprived female mice. METHODS One week after ovariectomy (Ovx) or sham operation,ICR female mice received daily injection of Pur (40 or 120 mg·kg-1, ip) or estradiol benzoate (EB, 4 μg·d-1,sc) for 4 weeks. Spatial memory was then tested by the water maze,and active avoidance paradigm was tested by shuttle-box, while the overall locomotor activity was monitored using open field. In additional, synaptic morphologic parameters were examined using electron microscopy and graph analyzer.RESULTS The distance to reach the platform was significantly reduced in Ovx mice treated with Pur at 120 mg·kg-1,and the number of active avoidance was increased by Pur of 120 mg·kg-1,when being compared to vehicle treated Ovx mice. The results from synaptic ultrastructural measurement and analysis did not show any differences in the length of active zones and the curvature of synaptic interface among sham, Ovx, and Ovx plus EB or Pur replacement mice. However, EB or Pur replacement effectively normalized the changes induced by Ovx, reducing the width synaptic cleft, enlarging the thickness of postsynaptic density (PSD) in the presynapse in both cerebral cortex Fr1 and hippocampus CA1 areas. CONCLUSION The beneficial effects of Pur on improving memory behavior of Ovx female mice are associated with the changes of some structural parameters of synapses, including the width of PSD and synaptic cleft in frontal cortex and hippocampus regions.
关键词
葛根素 /
雌激素 /
卵巢摘除 /
学习记忆 /
突触形态
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Key words
puerarin /
estrogen /
ovariectomy /
learning-memory /
synapse morphology
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徐晓虹.
葛根素对去卵巢小鼠学习记忆和突触结构的影响[J]. 中国药学杂志, 2008, 43(16): 1238-1242
XU Xio-hong.
Effects of Puerarin on Learning-Memory and Synaptic Structure in Ovariectomized Mice [J]. Chinese Pharmaceutical Journal, 2008, 43(16): 1238-1242
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脚注
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基金
浙江省自然科学基金(M303042);浙江师范大学博士基金项目
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