摘要
【目的】探讨邓铁涛教授健脑1方对血管性痴呆(VD)大鼠学习记忆能力的影响,并从分子生物学角度探讨其作用机制。【方法】采用双侧颈总动脉永久性结扎法复制VD动物模型,将60只SD雄性大鼠随机分为假手术组、VD模型组、中药高剂量组(剂量为57.6 g·kg-1·d-1)、中药低剂量组(剂量为14.4 g·kg-1·d-1)及尼莫地平组(剂量为5.4 mg·kg-1·d-1),给药30 d后采用Morris水迷宫检测各组大鼠的学习记忆能力,观察大鼠海马组织学改变,采用荧光定量法检测大鼠海马NR2B m RNA表达水平。【结果】水迷宫定位航行试验检测结果提示:第3天,与假手术组比较,模型组大鼠逃避潜伏期显著延长(P<0.05);第4天,中药高剂量组大鼠逃避潜伏期较模型组显著下降(P<0.05)。空间探索试验结果显示:60 s内中药高剂量组大鼠穿越平台的次数显著高于模型组,差异有统计学意义(P<0.01),各组停留在平台所在象限的时间与模型组比较差异均无统计学意义(P>0.05)。各组海马组织病理检查可见模型组大鼠海马CA1区神经细胞丢失,神经细胞核碎裂、核膜不清、核仁消失,神经细胞收缩,胞浆嗜酸性增强,胶质细胞反应性增生;中药高、低剂量组海马CA1区可见神经元细胞损伤,病变损伤程度均较模型组显著减轻。尼莫地平组、中药高剂量组NR2B m RNA的表达较模型组显著升高,差异均有统计学意义(P<0.05);中药低剂量组有增高NR2B m RNA表达的趋势,但差异无统计学意义(P>0.05)。【结论】健脑1方可显著改善血管性痴呆大鼠学习记忆能力,其作用可能与减少海马组织神经元损伤程度,上调海马NR2B m RNA表达有关。
Objective To observe the effect of Professor Deng Tietao＇s Brain-strengthening Recipe 1 on learning and memory abilities of rats with vascular dementia, and to explore its molecular biology mechanism. Methods The vascular dementia rat model was established by permanent occlusion of the bilateral arteria carotis communis. Sixty male SD rats were randomly divided into 5 groups, namely sham-operation group, model group, nimodipine（5.4 mg·kg-1·d-1） group, and high-and low-dose Chinese medicine groups（57.6 and 14.4g·kg-1·d-1, respecitvely）. After medication for 30 days, the learning and memory abilities were evaluated by Morris water maze test. The histological changes of the rat hippocampal tissues were observed after HE staining,and the m RNA expression of N-methyl-D-aspartate receptor subunit 2B（NR2B） in rat hippocampus was measured by real-time fluorescence quantitative polymerase chain reaction（RT-PCR）. Results The water maze test results showed that the escape latency of the rats in the sham-operation group was significantly decreased on the third day, and was significantly decreased in the high-dose Chinese medicine group on the fourth day（P〈0.05 compared with the model group）. The results of spatial probe test showed that the times of rats passing through the platform within 60 seconds were significantly higher in high-dose Chinese medicine group（P〈0.01compared with the model group）, but the time for rat staying at the quadrant of the platform in the other four groups did not differ from that in the model group（P〈0.05）. HE staining results for the model group were presented as the absence of neural cells in hippocampus CA1 region, karyorrhexis of nerve cells,indistinctness of nuclear membrane, disappearance of nucleolus, shrinkage of nerve cells, increase of cytoplasm acidophily, and reactive hyperplasia of astrocytes. And in the hippocampal CA1 region of high-and low-dose Chinese medicine groups, the injured neural cells were found, and the lesions were slighter than those of the model group. Compared with the model group, the mR NA expression of NR2B was increased in nimodipine group and high-dose Chinese medicine group（P〈0.05）. The mR NA expression of NR2B showed a increasing trend in low-dose Chinese medicine group, but the differences were insignificant compared with that of the model group（P〈0.05）. Conclusion Brain-strengthening Recipe 1 has obvious effects on improving the learning and memory abilities of vascular dementia rats, and the therapeutic mechanism is associated with reduction of the degree of neuronal damage in hippocampus and with the upregulation of the mR NA expression of NR2B.
出处
《广州中医药大学学报》
CAS
2015年第4期720-724,728,784,共7页
Journal of Guangzhou University of Traditional Chinese Medicine
基金
广东省科学技术厅立项资助项目(编号:2013B032500002)
广州中医药大学邓铁涛基金立项资助项目(编号:D201301)
关键词
血管性痴呆/中药疗法
健脑1方/药理学
基因表达调控
海马/病理学
疾病模型
动物
大鼠
Vascular dementia/TCD therapy
Brain-strengthening Recipe 1/pharmacology
Gene expression regulation
Hippocampus/pathology
Disease models
animal
Rats
