补肾方药对老年大鼠学习记忆相关信号分子mRNA表达的影响  

Effects of kidney-tonifying recipe on the expressions of learning and memory related signal molecules

作　　者：康湘萍[1] 金国琴[1] 梁超[2] 龚张斌[1] 张学礼[1] 戴薇薇[1] 

机构地区：[1]上海中医药大学基础医学院生化教研室,上海201203 [2]上海中医药大学基础医学院实验中医学教研室

出　　处：《中国老年学杂志》2013年第9期2064-2067,共4页Chinese Journal of Gerontology

基　　金：国家自然基金项目(No.30873317;81001565);上海市教育委员会重点学科建设项目(No.J50301);上海市教委预算内科研项目(2012JW03)

摘　　要：目的观察经典补肾方药——左归丸、右归丸对老年大鼠学习记忆相关信号分子糖皮质激素受体(GR)、N-甲基-D-天冬氨酸受体1(NR1)、N-甲基-D-天冬氨酸受体-2B亚基(NR2B)、钙调蛋白(CaM)、钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)-α、CAMP反应元件结合蛋白(CREB)及活性调节细胞骨架蛋白(Arc)mRNA变化的影响。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、老年糖皮质激素(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)。采用原位杂交法检测大鼠海马CA1、CA2-3分区GR、NR1及NR2B mRNA表达变化,实时定量PCR法观察海马组织CaM、CaMKⅡ-α、CREB及Arc mRNA表达变化及补肾方药对上述指标异常变化的改善作用。结果与青年对照组比较,老年大鼠海马GR、NR1、NR2B、CaM、CaMKⅡ-α、CREB及Arc mRNA表达均明显降低(P<0.05);补肾方药左归丸、右归丸及GR拮抗剂RU38486能不同程度地改善上述指标的异常变化。结论老年大鼠学习记忆能力减退可能与GR介导的学习记忆相关信号通路异常有关;补肾方药左归丸、右归丸及RU38486可能通过下调老年大鼠高水平皮质酮、上调学习记忆相关信号分子mRNA的表达,进而改善老年大鼠空间学习记忆能力。Objective To observe the effects of kidney-tonifying recipe-Zuogui pill and Yougui pill on the expressions of learning and memory related signal molecules （ GR, NR1, NR2B, CaM, CaMK II -a, CREB and Arc）. Methods The nature old SD rats were used as senile animal models. The rats were randomly divided into five groups： young（ aged 5 months） , senile （ aged 24 months） , senile ＋ antagonist RU38486 （ aged 24 months） , senile ＋ Zuogui pill（ aged 24 months） ,senile ＋ Yuogui pill groups （ aged 24 months）. Tile expressions of GR, NR1 , NR2B were examined by in situ hybridization method. The expressions of CaM, CaMK II -a, CREB and Arc in the hippocampus were tested by real-time quantitative PCR. The regulating effects of kidney-tonifying recipe on above indexes were also studied. Results Compared with young group, the expressions of mRNA-GR, NR1, NR2B, CaM, CaMK II-a, CREB and Arc were obviously decreased（P 〈 0. 05）. Kidney-tonifying recipe （Znogui pill, Yougui pill）and RU38486, however, could improve the abnormal changes of these indices in senile rats to varying degrees. Conclusions The deterioration of learning and memory abilities in senile rats may be partly related to abnormal transduction of the signal pathway which is mediated by GR. Kidney-tonifying recipe and RU38486 could improve spatial learning and memory abilities of senile rats through down-regnlating the higher CORT levels and retarding aging changes of the expressions of the related signal transduction molecules.

关 键 词：补肾方药 糖皮质激素 GR 信号转导 

分 类 号：R28[医药卫生—中药学]