补阳还五汤对血管性痴呆大鼠学习记忆和海马N-甲基-D-天冬氨酸受体表达的影响

目的观察补阳还五汤对血管性痴呆(VaD)大鼠海马CA1区N甲基D-天冬氨酸受体表达及长时程增强(LTP)的影响及机制。方法选择SD大鼠144只,随机分为假手术组、VaD模型组(模型组)、尼莫地平组和补阳还五汤组,每组36只。采用四血管阻断法制备VaD大鼠模型。Morris水迷宫实验评估大鼠学习记忆功能,大鼠海马CA3-CA1区记录海马CA1区LTP,免疫组织化学、Western blot法和实时荧光定量PCR检测大鼠海马NR1、NR2A、NR2B蛋白和mRNA表达的变化。结果与假手术组比较,模型组大鼠逃避潜伏期延长和平均探索次数减少(P<0.05),大鼠海马CA1区LTP明显降低(P<0.05),CA1区NR1、NR2A、NR2B蛋白及mRNA表达水平明显降低(P<0.05);与模型组比较,补阳还五汤组、尼莫地平组大鼠学习、记忆成绩明显提高(P<0.05),海马CA1区NR1、NR2A、NR2B蛋白及mRNA表达水平明显升高(P<0.05)。结论补阳还五汤可上调脑缺血再灌注海马CA1区脑组织NR1、NR2A、NR2B蛋白的表达,促进LTP,进而改善VaD大鼠学习记忆能力。

Effect of Buying Huanwu Tang on learning,memory and expression of NMDA receptors in hippocampus of rats with vascular dementia

Objective To study the effect of Buying Huanwu Tang(Decoction Invigorating Yang for Recuperation) on expression of NMDA receptors and LTPin hippocampal CAl area of rats with vascular dementia(VaD) and its mechanism.Methods One hundred and forty-four SD rats were randomly divided into sham operation group,VaD model group,nimodipine group,and Buying Huanwu Tang group(36 in each group).A rat VaD model was established by 4-vessel occlusion. Learning and memory of the rats were assessed by Morris water maze testing and recording the LTP in hippocampal CA3-CA1 area.Expressions of NR1,NR2A and NR2B proteins in hippocampal neurons were detected by immunohistochemistry,Western blot and RT-PCR,respectively. Results The escaping latency time(s) was longer,the average number of cross-platform exploration was less,the expression levels of NR1,NR2A,NR2B proteins and mRNA and LTP in hippocampal CA1 area were significantly lower in VaD model group than in sham operation group (P<0.05).The learning and memory scores were significantly higher in Buying Huanwu Tang group and nimodipine group than in VaD model group(P<0.05).No significant difference was found in learning and memory scores between Buying Huanwu Tang group and nimodipine group. Conclusion Buying Huanwu Tang can improve the learning and memory of rats by up-regulating the expression of NR1,NR2A,NR2B and LTP in hippocampal CA1 area.