川芎嗪对沙鼠前脑缺血-再灌注损伤后学习记忆的影响

目的探讨川芎嗪对沙鼠前脑缺血-再灌注后学习记忆的影响及其机制。方法40只蒙古沙土鼠随机分为4组。假手术组、脑缺血组、对照组、川芎嗪治疗组，每组10只。阻断沙土鼠双侧颈总动脉造成前脑缺血模型，4-FFF（4-pellet taking test）旱路迷宫法对沙鼠前脑缺血-再灌注7d后的学习记忆功能进行评定，HE染色方法观察海马CA1区神经元形态变化，免疫组织化学法观察海马CA1区胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）阳性星形胶质细胞的反应。结果假手术组未见坏死神经元，神经元密度（27．6±4．3）HS，脑缺血组中坏死神经元显著增多，神经元密度明显下将（6．8±1．7）HS（P〈0．05）；与脑缺血组比较，川芎嗪治疗组坏死神经元显著较少，神经元密度增加（16．9±2．6）HS（P〈0．05）。CA1区星形胶质细胞活性在脑缺血组中（7．7±1．8）HS明显高于假手术组（3．9±1．2）HS（P〈0．05）；与脑缺血组比较，川芎嗪治疗组星形胶质细胞活性进一步增强（P〈0．05）。4-PTT旱路迷宫实验显示。脑缺血组中沙鼠参照记忆指标和工作记忆指标与对照组有明显的差异（P〈0．05）；川芎嗪治疗组上述指标显著改善（P〈0．05）。结论川芎嗪能改善前脑缺血沙鼠的学习记忆能力，与其对星形胶质细胞活性调节有关。

Effect of Tetramethylpyrazine on learning - memory after forebrain ischemia - reperfusion injury in gerbils

Objective To investigate the effect and the possible protective mechanism of Tetramethylpyrazine（TMP） on learning-memory function after forebrain ischemiareperfusion injury in gerbils. Methods 40 gerbils were randomly divided into four groups ： sham operation group, isehemia group,ischemia ＋ NS treatment group and ischemia ＋ TMP treatment group. Transient forebrain ischemia model was formed by bilateral common carotid artery occlusion. The learning and memory function was evaluated 7d after isehemia-rePerfusion by 4-PTT dry path maze method. The changs of neuron morphous in hippocampal CA1 region were observed by HE staining. Astrocytes activity（ glial fibrillary acidic protein, GFAP） was measured by immunohistochemistry. Results No degenerated and necrotic neurons were found in sham group. The density of neurons in ischemia group（6.8 ± 1.7） was significantly decreased,as compared with that in sham group（27.6 ±4.3, P 〈0.05）. The density of neurons in TMP treatment group （16.9 ± 2.6）was obviously increased, as compared with that in ischemia group（ P 〈 0.05）. The levels of GFAP in ischemia group （7.7 ±1. 8 ） were significantly higher than those of sham group （3.9 ±1.2, P 〈 0. 05） ; the levels of GFAP in TMP treatment group were obviously higher than that of ischemia group（ P 〈 0.05 ）. There were significant differences in the indexes of reference-memory and working memory between sham group and ischemia group. The indexes in TMP treatment group were improved obviously （ P 〈 0.05）. Conclusion TMP can improve the learning-memory function after forebrain ischemia reperfusion damage in gerbils. One of molecular mechanisms is related to its regulation effects on astrocytes activity.