补肾方药延缓老年大鼠学习记忆减退的分子机制

目的:观察补肾方药左归丸、右归丸对老年大鼠空间学习记忆能力,氨基酸神经递质以及NMDA受体、Ca2+/CaMKⅣ信号通路相关分子的mRNA表达变化的影响,以探讨老年大鼠学习记忆减退的分子机制以及补肾方药的药理作用。方法:以青年大鼠(5月龄)为对照,以自然衰老大鼠(23月龄)为模型;Morris水迷宫法观察大鼠空间学习记忆能力;HPLC-荧光法检测大鼠杏仁核、海马氨基酸类神经递质含量;RT-PCR法检测大鼠海马NR1、CaMKⅣ、CREB、c-fos mRNA的表达变化;观察补肾方药左归丸、右归丸对老年大鼠上述各项指标的影响。结果:与青年对照组比较,老年大鼠上述指标都有不同程度的异常变化,而左归丸、右归丸可改善老年大鼠退化的空间学习记忆能力;降低老年大鼠杏仁核、海马Glu的含量;显著上调老年大鼠NR1、CaMKⅣmRNA的表达,对CREB及c-fos mRNA的表达也有升高。结论:左归丸、右归丸可以通过降低老年大鼠杏仁核、海马Glu含量,纠正NMDA受体介导的CaMKⅣ信号通路的异常变化,改善老年大鼠空间学习记忆能力,延缓衰老。

Molecular mechanism of kidney-tonic decoction in attenuated learning and memory of old rats

Objective：To observe the effect of the kidney-reinforcing decoction Zuoguiwan and Youguiwan on spatial memory, content of amino acid neurotransmitter,NMDA receptor and the key molecule of the signal transduction pathway-Ca^2＋/CaMKⅣ in old rats for exploring the possible molecular mechanisms and therapeutic effect of this drugs. Methods ： The research was based on the younger rats（ controls,aged 5 months old） and animal models （naturally aged,23 months old）. Morris water maze was used to examine the ability of spatial leaning and memory and HPLC-fluorometric method was employed to measure the content of Glu in amygdala and hippocampus from the rats. RT-PCR was used to detect the expression of NR1 ,CaMKⅣ, CREB and c-los mRNA in hippocampus. In addition,observed were the kidney-reinforcing decoction Zuoguiwan and Youguiwan on the factors described above. Results： Compared with the controis,some abnorulal changes were observed in the involved factors in old rats. The decoction Zuoguiwan and ~ouguiwan could improve the ability of spatial leaning and memory of old rats by lowering the content of Glu, up-regulating the mRNA expression of NR1, CaMKⅣ, CREB and c-los to a certain degree. Conclusion ： The kidney-reinforcing decoction Zuoguiwan and Youguiwan can improve the ability of spatial leaning and memory in old rats through reducing the Glu content in brain, modifying the abnormal signal transduction pathway of Ca^2 ＋/CaMKⅣ mediated by NMDA receptor, thus delaying the aging process.