乌龙丹改善慢性脑缺血大鼠学习记忆功能的分子机制探讨

Molecular mechanism of Wulongdan for improving the learning and memory abilities of rats with chronic cerebral ischemia

目的通过建立大鼠慢性脑缺血模型,观察NR1、NR2B在海马和皮层的表达水平,探讨乌龙丹改善慢性脑缺血大鼠学习记忆功能的部分作用机制。方法采用双侧颈总动脉永久性结扎制作大鼠慢性脑缺血模型,造模3周后存活大鼠随机分为假手术组、模型组、银杏叶组、乌龙丹高剂量组、乌龙丹低剂量组(n=12),Morris水迷宫检测大鼠学习记忆能力,Western blot法检测大鼠海马和皮层NR1、NR2B的表达水平。结果模型组大鼠学习记忆能力较假手术组和乌龙丹给药组明显降低(P<0.05,或P<0.01);模型组皮层及海马区NR1、NR2B表达水平与假手术组比较,比值显著降低(P<0.01)。乌龙丹高剂量组和银杏叶组皮层及海马与模型组比较NR1、NR2B表达均增高(P<0.01);但与假手术组比较,NR1、NR2B表达水平比值降低,差异也具有统计学意义(P<0.01)。结论乌龙丹改善大鼠慢性脑缺血学习记忆功能可能途径之一:一定程度上提高海马和皮层区NR1、NR2B的表达水平。

Objective To evaluate the effect of Wulongdan on the learning and memory abilities of rats with chronic cerebral ischemia and explore the mechanisms.Methods Male SD Rat models of chronic cerebral ischemia were established by permanent ligation of the bilateral carotid arteries.Three weeks after the operation,the rats were randomly divided into sham-operated group,chronic cerebral ischemia group（model group）,high-dose drug group,low-dose drug group and Yinxingye group and received the corresponding treatments on a daily basis for5 consecutive weeks.Morris watermaze was used to assess the learning and memory abilities of the rats,and Western blotting was carried out fordetecting the expressions of NR1 and NR2B in the hippocampus and cerebral cortex.Results Compared with the model group,the rats in high-dose drug,low-dose drug and Yinxingye groups showed significantly shorter time of finding platform in Morris water maze test（P0.05 or0.01）.The rats in the model group showed significantly lowered expressions of NR1 and NR2B of the cortex and hippocampus than those in the sham-operated group（P0.01）.In comparison with the model group,the high-dose Wulongdan group and Yinxingye group both showed significantly increase expressions of NR1 and NR2B（P0.01）,but their expression levels still remained significantly lowerthan those in the sham-operated group（P0.01）.Conclusion Wulongdan can enhance the learning and memory abilities of rats with chronic cerebral ischemia,the mechanisms of which may involve increased expressions of NR1 and NR2B in the hippocampus and cortex.