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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
OBJECTIVE: To evaluate the efficacy of ligustrazine on cognitive impairment after cerebral ischemia in a rat model and its possible mechanism. Methods Ninety healthy elderly Wistar rats with active response avoidance (AAR) ≥80% were trained in the shuttle box for 7 days and randomly divided into control group, cerebral ischemia group and ligustrazine group. A rat model of vascular dementia was established by modified Pulsinelli’s four-vessel occlusion (4VO) method; learning and memory function was detected by computer-controlled shuttle box system and hippocampal slices induced long-term potentiation (LTP) in the CA1 region; Hybridization method was used to detect the expression of NMDAR1 mRNA in rat hippocampus. The tetramethylpyrazine was injected intraperitoneally within 4 min after 4VO. Results The AAR of cerebral ischemic (BI) rats was (60±5)% at 2 weeks compared with 90%±5% of control (CO) groups (t=1.852, P<0.05). AAR in the (BI) group rats was 40% ± 8% at 4 weeks and 2 months, respectively, 41% ± 8% compared with CO group 92% ± 6%, 91% ± 6% decreased more significantly (t =2.947,3.504,P<0.01); Ligustrazine (TMP) group at each time point AAR and BI group were significantly improved (t=1.803, P<0.05). LTP waveforms were significantly induced in both CO and TMP groups; LTP was almost unattractable in all phases of BI group, and the percentage change of field excitatory postsynaptic potential (fEPSP) before and after conditional stimulation was compared with that of CO and TMP groups. The difference was significant (t=4.064, 3.655, P<0.01), but there was no significant difference between the time points. The expression of N-methyl-D-aspartate receptor 1 (NMDAR1) mRNA in CA1 and CA3 regions in BI group was higher than that in normal control group at 2 weeks, but decreased at 4 and 2 months; TMP group and BI group There are significant differences. Knot