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银杏叶提取物对点燃幼鼠学习记忆、神经元凋亡和神经发生的作用研究

Effect of extract of Ginkgo bilob on learning and memory, neuron apoptosis and neurogenesis of juvenile rats with kindled seizure
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摘要 目的探讨银杏叶提取物(EGb)对癫痫点燃幼鼠学习记忆及神经元凋亡、神经发生的影响。方法选择21d日龄SD大鼠若干只,按照随机数字表法分为生理盐水组(NS)、点燃对照7d组(P—A7组)、点燃对照14d组(P—A14组)、EGb治疗7d组(P-E7组)、EGb治疗14d组(P-E14组),每组48只。应用戊四氮(PTZ)诱导点燃模型,Morris水迷宫检测大鼠学习记忆水平的变化,免疫组化法观察大鼠海马细胞凋亡、增殖情况,Brdu/神经元核抗原(NeuN)、BrdU/胶质纤维酸性蛋白(GFAP)荧光双标观察神经元分化的结果。结果(1)Morris水迷宫测试显示第4天时P-E7和P-E14组大鼠逃避潜伏期较NS组、P-A7组、P-A14组明显缩短,差异有统计学意义(P〈0.05);靶象限活动时间百分比较P-A7组、P-A14组大鼠明显上升,跨越平台次数明显增多,差异有统计学意义(P〈0.05)。(214组点燃大鼠海马CA3区TUNEL阳性细胞明显多于NS组,而P-E7和P-E142组大鼠凋亡细胞数较相应的P-A7、P—A14组明显减少,差异均有统计学意义(P〈0.05)。(3)4组点燃大鼠海马CA1、CA3和DG区内巢蛋白(nestin)阳性细胞数量较NS组明显增多,差异有统计学意义(P〈0.051,其中尤以P—E7和P-E14组为著。大部分nestin阳性细胞向NeuN+细胞转化,BrdU/GFAP共表达率仅为4%~5%。结论EGb可以明显改善点燃幼鼠的学习记忆功能,推测机制为EGb的抗凋亡作用及诱导神经干细胞增殖、分化的作用。 Objective To study the effect of extract of Ginkgo bilob (EGb) on learning and memory, nerve cell apoptosis and neurogenesis of juvenile rats with kindled seizure. Methods Two hundred and forty 21-d old SD rats were equally randomized into normal saline group (NS), kindled control for 7 d group (P-A7), kindled control for 14 d group (P-A14), EGb treatment for 7 d group (P-E7), EGb treatment for 14 d group (P-E14). All the rats, except rats of the NS group, were induced chronic kindling seizure by pentylenetetrazol. Morris maze test was used to detect the learning and memory abilities. Immunohistochemical staining was used to observe the nerve cell apoptosis and neural stem cell proliferation and differentiation in the hippocampus. BrdU/NeuN or BrdU/GFAP double-labeled staining was employed to observe the nerve cell differentiation. Results (1) The escape latency in Morris maze test in rats of every group was gradually shorted during 4 days of pre-treatment; the escape latency was (31.72±8.37) in P-E7 group and (31.29±4.35) in P-E14 group, which was significantly shorten than that in NS group (18.93±6.40), P-A7 group (47.86±9.14) and P-A14 group (44.79±7.72) (P〈0.05); the time in target quadrant in maze test showed gradual increase in rats of the NS, P-A7 and P-A14 groups and was significantly increased in rats of the P-E7 and P-E14 groups after EGb treatment (P〈0.05); the cross-platform times of rats in the P-A7 and P-A14 groups (4.38±1.06, 4.50±0.93) in maze test were significantly shorter than those of NS rats (11.13±0.99), P-E7 rats (10.00±2.00) and P-E14 rats (10.63±0.92, P〈0.05). (2) TUNEL-positive cells in CA3 area of hippocampus in rats of the NS group were obviously fewer than those in the other 4 groups (P〈0.05). The number of apoptotic cells in P-E7 and P-E14 groups was (28.25±4.65) and (28.13±6.08), which was significantly reduced as compared with that in the P-A7 and P-A14 groups (P〈0.05). (3) Nestin-positive cells in the hippocampal CA1, CA3 and DG regions of rats from the NS group were fewer than those in the other 4 groups (P〈0.05); those in the P-E7 and P-E14 groups enjoyed the highest levels. (4) The number of BrdU/NeuN cells after EGb treatment was significantly larger than that before EGb treatment, and BrdU/NeuN-positive cells percentage in P-E14 group was higher than that in P-E7 group (P〈0.05), meanwhile, the co-expression of BrdU/GFAP was about 4%-5% after EGb treatment. Conclusion EGb can significantly improve the learning and memory abilities in young rats with kindled seizure; anti-apoptosis and promoted neural stem cell proliferation and differentiation effect of EGb might be the mechanism.
出处 《中华神经医学杂志》 CAS CSCD 北大核心 2012年第11期1131-1137,共7页 Chinese Journal of Neuromedicine
关键词 银杏叶提取物 癫痫 学习记忆 神经发生 Extract of Ginkgo bilob Epilepsy Learning and memory Neurogenesis.
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