葛根素对雌激素剥夺小鼠学习记忆行为的影响

Effects of puerarin on learning-memory behaviour in estrogen-deprived female mice

目的研究葛根素对雌激素剥夺小鼠学习记忆功能的影响。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,50,100 mg·kg-1,ip)或苯甲酸雌二醇(EB,1,5 μg·d-1,ip)治疗。分别用Y-迷宫和水迷宫检测小鼠的分辨学习记忆和空间记忆行为:高效液相色谱分析大脑前皮层和海马组织的谷氨酸(Glu)和γ-氨基丁酸(GABA)含量。结果Ovx小鼠经50或100 mg·kg-1Pur治疗后,在Y-迷宫达到学会标准所需训练次数分别下降11.8%和17.8%(P>0.05和P<0.05),记忆保持率分别提高23.3%和28.3%(P<0.05)。因Ovx而延长的水迷宫平台搜寻潜伏期缩短15.5%和23.8% (P<0.05)。同时,100 mg·kg-1Pur使Ovx小鼠海马组织的Glu和GABA水平恢复正常,Glu从Ovx小鼠的(24.1±4.5)mg·g (pro)-1回升到(27.9±3.5)mg·g(pro)-1(P<0.05),而GABA则从(5.64±1.06)mg·g(pro)-1回调到(4.73±0.85)mg·g(pro)-1 (P<0.05)。结论长期Pur治疗可通过影响海马谷氨酸能和GABA能递质系统改善雌激素剥夺引起的记忆损伤,该作用可能与Pur的植物雌激素样活性有关。

OBJECTIVE: To study the protective effects of puerarin (Pur) on learning and memory in estrogen-deprived female mice. METHODS: One week after ovariectomy (Ovx) or sham operation, female mice were given a 4-week treatment of Pur (50 or 100 mg &middot kg-1, ip) or estradiol benzoate (EB, 1 or 5 μm &middot d-1, ip). Discriminating learning and memory performance was tested using Y-maze, and spacial memory was detected using water maze. After behavior test, levels of glutamate (Glu) and GABA in fore-cortex and hippocampus were assessed using high performance liquid chromatography (HPLC). RESULTS: Following the treatment of 50 or 100 mg &middot kg-1 Pur in Ovx mice, the training times achieved learning criterion in Y-maze declined by 11.8% and 17.8% (P > 0.05 and P -1 Pur normalized the levels of Glu and GABA in the hippocampus of Ovx mice, and Glu level was significantly elevated from (24.1 ± 4.5) to (27.9 ± 3.5) mg &middot g(pro)-1 (P -1 (P < 0.05). CONCLUSION: Long-term treatment of Pur ameliorated learning and memory deficit of Ovx mice through affecting the activity of glutamatergic/GABAergic system in hippocampus. The phytoestrogen activity of Pur may contribute to its protective effects on memory dysfunction induced by estrogen-deprived.