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目的:从糖皮质激素受体-脑源性神经营养因子-NMDAR(GCR-BDNF-NMDAR)信号转导通路角度,探讨老年大鼠学习记忆退化的分子机制及补肾方药——左归丸、右归丸的调整作用。方法:以自然衰老(24月龄)SD雄性大鼠为动物模型,随机分为老年对照组、老年皮质酮(GC)拮抗组、老年左归组和老年右归组,另设一组青年对照组(5月龄)。采用ELISA法检测大鼠血清皮质酮含量、Morris水迷宫法观察大鼠空间学习记忆能力、电生理方法记录在体大鼠LTP变化,Western Blot及免疫组化法观察大鼠学习记忆相关信号转导蛋白表达变化,同时观察补肾方药对上述指标变化的改善作用。结果:与青年对照组相比,老年大鼠血清皮质酮含量显著升高、空间学习记忆能力显著下降(P<0.05)、海马CA1区LTP明显受到抑制、与学习记忆相关的信号分子蛋白表达均明显降低(P<0.05),左归丸、右归丸能不同程度地改善上述指标的衰老性变化。结论:左归丸、右归丸改善老年大鼠增龄性学习记忆退化的部分机制可能与提高GCR、BDNF、NMDAR、钙/钙调素依赖性蛋白激酶Ⅱ(CaMKⅡ)、细胞外调节蛋白激酶(ERK1/2)、CAMP反应元件结合蛋白(CREB)蛋白表达,拮抗高水平皮质酮对大脑海马区域的毒性作用有关。
OBJECTIVE: To investigate the molecular mechanism of learning and memory degeneration in senile rats and the prescriptions of tonifying kidney - Zuo Gui Wan, from the perspective of the signal transduction pathway of glucocorticoid receptor-brain derived neurotrophic factor-NMDAR (GCR-BDNF-NMDAR) Regulate the role of pill. Methods: A natural aged (24-month-old) male SD rats were randomly divided into three groups: old control group, old-aged corticosterone antagonist group, aged Zuogui group and old age group, Group (5 months old). Serum corticosterone levels were measured by ELISA. Spatial learning and memory ability of rats was observed by Morris water maze test. Changes of LTP in rats were recorded by electrophysiological method. Western Blot and immunohistochemistry were used to observe the signal transduction of learning and memory Protein expression changes, while observing Bushen Fang on the improvement of these indicators. Results: Compared with the young control group, the content of serum corticosterone in the aged rats was significantly increased (P <0.05), the LTP in the hippocampal CA1 region was significantly inhibited, and the expression of the protein related to learning and memory (P <0.05). Zuogui Wan and Yougui Wan can improve the above senescence changes to some extent. Conclusion: Zuogui pill and Yougui pill may ameliorate aging-induced learning and memory impairment in aged rats may be related to the increase of GCR, BDNF, NMDAR, CaMKⅡ, extracellular regulated protein kinase (ERK1 / 2), CAMP response element binding protein (CREB) protein expression, to antagonize the high level of corticosterone on the brain hippocampus region toxicity.