血塞通对 MCAO 大鼠不同恢复时间点Nogo-A 蛋白表达的影响

目的：探讨血塞通冻干粉注射液对大鼠局灶性脑缺血模型不同恢复时间点7d，14d，28d大脑皮层的主要抑制因子Nogo-A表达的影响。方法健康雄性SD大鼠，随机分为手术组和非手术组，手术组采用改良Longa方法建立大脑中动脉阻塞（ MCAO）模型，待大鼠术后清醒2h后，进行EZLonga评分，根据评分和体重随机分为血塞通大剂量组（7．2mg／100g）、小剂量组（3．6mg／100g）、尼莫地平组（1．44mg／100g）、模型组（生理盐水），于手术当日开始给药。待7d，14d，28d时，各组取6～8只动物，迅速取脑，于视交叉处将大脑前后分开，前端脑放入10％的甲醛中固定，48h后用PBS将脑组织洗净，石蜡包埋切片，用免疫组织化学染色方法观察不同时间点Nogo-A的表达变化，分别对梗死区、梗死周边区进行平均光密度分析。结果梗死区随着时间的延长，Nogo-A的表达逐渐减弱，在各时间点内，血塞通组和尼莫地平组Nogo-A的表达高于模型组。梗死周边区，模型组Nogo-A的表达趋势是7 d时已经高表达，14 d达到高峰，28 d比14 d略低，但仍保持较高水平，在各时间点，血塞通组比同时间点内的模型组表达低，与模型组差异显著（P＜0．05）。结论血塞通可以保护大鼠梗死区及梗死周边区的神经细胞，可以下调梗死周边区不同恢复时间点Nogo-A的表达。血塞通可能是通过下调Nogo-A的表达来实现大脑神经功能的重塑重建作用。

Effect of Xuesaitong on Expression of Nogo-A Protein in MCAO Rats at Different Recovery Time

Objective To evaluate effect of Xuesaitong on expression of Nogo-A Protein in MCAO rats at 7th,14th and 28th day after recovery.Methods Normal male SD mice were randomly divided into operation group and nonoperation group.The modified Longa method was used to establish MCAO models and the EZLonga evaluation was made after waking up for 2 hours.Based on the evaluation and weight,the rats were randomly divided into high-dosage of xuesaitong group, low-dosage of xuesaitong group, nimodipine group and model group,they were administrated on the same day as the operation.After the operation,6-8 animals on the 7th,14th,and 28th day were select-ed from each group and their brain were brought out.The brains were cut into two parts at optic chiasm and the front parts were put into 10%formalin.After 48h,the front parts of the brain were washed with PBS.Tissue were embedded in paraffin and the expression of at different time points were observed through immunohistochemical staining method.Average optical density analysis of infarction area and borderline area were made.Results Nogo-A expression in infarction area gradually decreased with the time prolonged.The expression of Nogo-A in xuesai-tong group and nimodipine group was higher than that in model group.In the infarct borderline area,the expression of Nogo-A was high on the 7th day,the highest on the 14th day,while the expression of Nogo-A on the 28th day was lower than that on the 14th day but also on a high level.Besides,the expression of Nogo-A in Xuesaitong group was lower than that in model group at any time points and the difference was statically significant（P〈0.05）.Conclusion Xuesaitong can not only protect nerve cells in infarction area and its peripheral area but also can reduce the expression of Nogo-A in infarction peripheral area at different time points.Xuesaitong may protect and reconstruct brain func-tion by reducing the expression of the Nogo-A.