补肾方药对老年大鼠学习记忆退化的影响

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(P0.05)、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(P0.05),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。

Degradation mechanisms of learning and memory in aging rats and the effects of kidney-tonifying recipe

Objective: To observe the effects of Kidney-Tonifying Recipe-Zuogui Wan and Yougui Wan on the learning and memory related signal transduction(GCR-BDNF-NMDAR).Methods:The nature old SD rats were used as senile animal model.They were randomly divided into five groups: young group(aged 5 month),senile group(aged 24 month),senile + antagonist RU38486(aged 24 month),senile + Zuogui Wan group(aged 24 month) and senile + Yuogui Wan group(aged 24 month).The contents of serum CORT were examined by the enzyme-linked immunosorbent assay(ELISA).The spatial learning and memory abilities were observed by Morris water maze test.The changes of LTP were tested by electrophysiological method.The expressions of related signal transduction proteins were tested by Western blot and immunohistochemistry method.The regulating effects of kidney-tonifying recipe on above indices were also studied.Results:Compared with young group,the contents of CORT in serum of senile rats were obviously increased.The spatial learning&memory abilities and LTP were lower than those in the young group markedly.And the expressions of learning and memory related signal transduction proteins were obviously decreased.Zuogui Wan and Yougui Wan,however,could improve the abnormal changes of these indices in senile rats to varying degrees.Conclusion:Kidney-tonifying recipe could improve spatial learning and memory abilities of senile rats through down regulating the higher CORT levels and retarding the expressions of related signal transduction proteins.