雌二醇对去卵巢大鼠学习记忆能力及脑内氨基酸水平的影响

Effects of Estradiol on Learning and Memory in Ovariectomized Rats:Relationship with the Contents of Amino Acids in the Cerebrum

目的:研究雌二醇对去卵巢大鼠学习记忆能力及脑内氨基酸水平的影响。方法:采用双侧卵巢切除术(ovariectomy,OVX)建立大鼠雌激素缺乏模型,雌二醇组于OVX后第7周每日皮下注射(sc)雌二醇75,300μg.kg-1至第16周,假手术组与模型组每日sc 0.5 mL.kg-1溶剂。第15周通过Morris水迷宫检测大鼠的学习记忆能力,第16周处死大鼠,用高效液相色谱法测定大鼠前皮层和海马的4种氨基酸的含量。结果:与假手术组相比,模型组大鼠学习记忆能力明显下降,前皮层和海马谷氨酸(glutamic acid,Glu)含量及谷氨酸/γ-氨基丁酸(glutamicacid/γ-aminobutyric acid,Glu/GABA)明显下降;与模型组相比,雌二醇75μg.kg-1治疗组,学习记忆能力明显改善,其前皮层和海马Glu含量及Glu/GABA明显升高;而雌二醇300μg.kg-1治疗组大鼠学习记忆能力无明显改善,其前皮层Glu/GABA明显增加,但海马Glu/GABA无明显变化。结论:雌二醇75μg.kg-1改善去卵巢大鼠的学习记忆能力的作用,可能与其增加脑内海马Glu/GABA比值有关。

Objective：To investigate the influence of estradiol on learning and memory and the content of amino acids in the cerebrum of ovariectomized rats. Methods：Adult female rats were treated daily with subcutaneous injection of estradiol （75,300 μg ·kg^-1） or the solvent （0.5mL.kg^-1） between weeks 7 and 16 after ovariectomy （OVX） or sham operation. The learning and memory of the rats was tested by a Morris water maze task on week 15, after which they were sacrificed and the content of amino acids in the cerebrum measured with high performance liquid chromatography （HPLC）. Results：The ability of learning and memory was significantly declined, and the content of glutamic acid and the ratio of glutamic acid to γ-aminobutyric acid （Glu/GABA） in prefrontal cortex and hippocampus of OVX group was significantly decreased as compared to those of sham group. In addition,the ability of learning and memory of estradiol （75 μg ·kg^-1） treated group was significantly improved and the content of Glu and Glu/GABA in prefrontal cortex and hippocampus were significantly increased as compared to those of OVX group. However, the Glu/GABA ratio remained unchanged in the hippocampus of estradiol （300 μg ·kg^-1） treated group as compared to that of OVX group;and the ability of learning and memory in these rats did not significantly improve. Conclusion： Estradiol （75μg ·kg^-1） improves the ability of learning and memory in OVX rats, and the increased Glu/GABA ratio in hippocampus possibly contributes to such an effect.