川芎嗪改善脑缺血后学习记忆障碍的实验研究(英文)

目的通过利和大鼠模型对中药川芎嗪对脑缺血后认知障碍的疗效进行评价,探讨其可能的机制。方法选用主动回避反应(AAR)≥80%的健康老龄Wistar大鼠90只进行7d穿梭箱训练后以随机数字表法分为对照组、脑缺血组、川芎嗪组。用改良Pulsinelli's四血管阻断(4VO)法建立血管性痴呆大鼠模型;采用电脑控制的穿梭箱系统和海马脑片诱导的CA1区长时程增强(LTP)检测大鼠学习记忆功能;原位杂交方法检测大鼠海马NMDAR1mRNA的表达;在大鼠4VO后5min内腹腔内注射川芎嗪,观察上述指标变化。结果脑缺血(BI)组大鼠的AAR在2周时为(60±5)%较对照(CO)组90%±5%有所下降(t=1.852,P<0.05),脑缺血(BI)组大鼠的AAR在4周和2个月时分别为40%±8%,41%±8%较CO组92%±6%,91%±6%有所下降更加明显(t=2.947,3.504,P<0.01);川芎嗪(TMP)组各时相点AAR与BI组比较均有明显改善(t=1.803,P<0.05)。CO组和TMP组均可明显诱出LTP波形;BI组各时相点均几乎诱不出LTP,条件刺激前后场兴奋性突触后电位(fEPSP)斜率变化的百分数与CO组和TMP组比较差异有显著性意义(t=4.064,3.655,P<0.01),但各时相点间差异无显著性意义。BI组2周时CA1和CA3区N-甲基-D-天冬氨酸受体1(NMDAR1)mRNA表达较正常对照组增高,但4周和2个月时表达减低;TMP组与BI组比较有明显差别。结

Therapy effect of tetramethylphrazim on cognitive impairment after cerebral ischemic injury

Aim To evaluate the therapeutic effect of active avoidance response on impairment of learning and memory ability after cerebral ischemic injury.Methods 90 Wistar rats were randomly divided into three groups:the control group,the brain ischemic group and TMP-treated group.Each group was observed at 3 time points:the 2nd week,the 4th week and the 2nd month after ischemia.The VD rat model was established by four-vessel occlusion(4VO).The changes of memory ability, LTP and the NMDAR1mRNA expression in the hippocampus were administered by computerized shuttle-training case, extracorporeal hippocampal slices method and in situ hybridization.TMP was injected into abdominal cavity within 5 minutes after the cerebral reperfution.Results Compared with the control group (2nd week:90%± 5% ;4th week:92%± 6% ;2nd month:91%± 6% ),the AAR in the brain ischemic group was significantly lower in the 2nd week(60%± 5% ), the 4th week (40%± 8% ) and the 2nd month (41%± 8% ) (t=1.852,P< 0.05),and it was more obviously at the later two time points(t=2.947,3.504,P< 0.01). In comparison with the brain ischemic group, the AAR of TMP-treated group was absolutely improved(t=1.803,P< 0.05).In the slices of extracorporeal hippocampal CA1 region,LTP detection showed that its injury had happened clearly in brain ischemic group at each time point of the 2nd week,the 4th week and the 2nd month.LTP wave could induce significantly in CO group and TMP group;LTP wave could hardly induce at each time point in BI group.Comparing the percentage of fEPSP slope changes before and after conditioned stimulation,there was a significant difference between CO group and TMP group(t=4.064,3.655,P< 0.01),but no significant difference among each time points; at the 4th week and the 2nd month,it was decreased in each region.Compared with brain ischemic group, significant changes were found in the TMP-treated group at each time point.Conclusion In the early phase of ischemic re-perfusion, TMP can improve impairment of learning and memory.