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低剂量木黄酮降低缺血后神经元损伤并改善学习记忆功能
Low dose of genistein attenuates neuronal injury and improves learning and memory functions of rats following global cerebral ischemia
目的 探讨染料木黄酮 (GEN) 对全脑缺血 (GCI) 大鼠海马CA1区神经元的神经保护作用及其可能的机制。方法 建立大鼠4动脉结扎全脑缺血模型，实验动物随机分为假手术组（sham）、缺血再灌注组 (I/R)、GEN处理组、ICI 182,780组和溶剂对照组。采用Fluoro-Jade B和神经元特异性核蛋白(NeuN)染色观察海马CA1区神经元存活情况，TUNEL技术观察海马CA1区神经元的凋亡。Morris水迷宫观察大鼠的空间学习和记忆功能。结果 GEN发挥神经保护作用的最佳剂量为1.0 mg/kg；与sham组相比，I/R组和溶剂对照组海马CA1区TUNEL阳性神经元数量显著增多（P <0.01），而1.0 mg/kg GEN可显著降低缺血后TUNEL阳性神经元数量 (P<0.01)；与I/R组相比，GEN能明显改善缺血后大鼠的空间学习和记忆能力。缺血前侧脑室给予ICI 182,780可显著降低GEN的神经保护作用 (P<0.01)。
结论 低剂量 (1.0mg/kg) GEN可显著降低缺血后大鼠海马CA1区神经元损伤，改善认知功能，其分子机制可能与雌激素受体活性密切相关。
Objective To explore the neuroprotective role of Genistein (GEN) on hippocampal CA1 neurons and the possible mechanism following global cerebral ischemia (GCI) in rats. Methods Seventy five rats were subjected to global cerebral ischemia (GCI) by four-vessel occlusion and randomly divided into five groups, sham, ischemia/reperfusion (I/R), GEN, ICI 182,780 and vehicle groups. Fluoro-Jade B and neuron-specific nuclear-binding protein (NeuN) staining was used to observe CA1 neuronal survival. TUNEL was used to detect apoptotic neurons. Spatial learning and memory function of the rats were evaluated by Morris water maze. Results The best dose of neuroprotective role of GEN was 1.0mg/kg body weight. Compared with sham, TUNEL-positive neurons in the hippocampal CA1 region increased significantly in I/R and vehicle groups (P<0.01), while posttreatment with GEN (1.0mg/kg) at 5min after ischemia by tail vein injection decreased markedly (P<0.01). Treatment of 1.0mg/kg GEN markedly attenuated spatial learning and memory deficits of the rats after ischemic insult compared to I/R group. Furthermore, ICI 182,780 significantly abolished the neuroprotective role of GEN (P<0.01). Conclusion The low-dose (1.0mg/kg) GEN significantly attenuates neuronal damage and cognitive deficits following GCI in rats, and the mechanism may be involved in estrogen receptor activity.
木黄酮 / 脑缺血/再灌注 / 海马CA1区 / 雌激素 / 原位缺口末端标记 / 大鼠
Genistein / Ischemia/reperfusion / Hippocampal CA1 region / Estrogen / Terminal UTP nick end labeling / Rat
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