Abstract: Objective To observe the therapeutic effect of Zhuyu Tongmai Capsule on motor dysfunction induced by middle cerebral artery occlusion ( MCAO) and cerebral ischemia-reperfusion in rats and to study its mechanism. Method The model of middle cerebral artery occlusion ( MCAO) was established by thread occlusion in rats. According to the neural symptom scores of the model animals, the rats were randomly divided into 5 groups after 24 hours: the model group, Zhuyu Tongmai 200, 100, 50 mg / kg group, Ginkgo Leaf Tablets group, and the sham operation group. The rats were administrated by gavage for 14 days. The running test of rats was carried out with gas-2 gait instrument, and the dynamic images of rats’ gait were analyzed. The expression of VEGF, IL-1β, TNF-α in serum was detected by ELISA. Histopathological analysis was carried out in the motor sensory area and hippocampal area of the ischemic side of the brain to observe the neuron damage by HE staining. The expression of nestin and synaptophysin in the ischemic side of the brain was detected by immunohistochemistry. Result Compared with the model group, each dose of Zhuyu Tongmai Capsule can significantly increase the walking speed of the model animals and the average walking cycle; increase the limb stride; reduce the absolute average body angle; reduce four limbs walking cycle,support time and swing time; reduce the braking time and propulsion time of four limbs. On the 14^th day after the establishment of the rat model, Zhuyu Tongmai Capsule (200 mg / kg) could enhance the expression of nestin protein in the area around the cortex infarction, but each dose had no significant effect on the content of VEGF, TNF-α and synaptophysin ( SYP ) . Conclusion Zhuyu Tongmai Capsule can significantly promote the recovery of limb motor function in rats with middle cerebral artery occlusion cerebral ischemia, and its mechanism may be related to the enhancement of Nestin protein expression in the area around cerebral infarction, increase of serum VEGF and decrease of serum IL-1β trend,so as to reduce nerve cell injury and promote its neurogenesis of the brain.

Key words: Zhuyu Tongmai Capsule, artery occlusion, cerebral ischemia-reperfusion, motor dysfunction

摘要： 目的 观察逐瘀通脉治疗给药对大鼠大脑中动脉阻塞脑缺血再灌注致运动功能障碍的影响及机制研究。方法 线栓法建立大鼠大脑中动脉阻塞(MCAO)模型,24 h 后按动物神经症状评分随机分为 5 组:即模型组、逐瘀通脉 200、100、50 mg / kg 组、银杏叶片组;另设假手术组。 动物灌胃给药 14 d,采用 GAS-2 步态仪对大鼠进行跑步测试,分析大鼠步态的动态图像。 ELISA 法检测血清中 VEGF、IL-1β、TNF-α 的表达。 对脑组织缺血侧皮层运动感觉区和海马区进行病理组织学分析,HE 染色观察神经元损伤情况,免疫组化法检测缺血周围区脑组织中缺血侧nestin 以及突触素的表达。 结果 与模型组比较,逐瘀通脉各剂量可明显提高行走速度,增加平均步行周期和四肢步幅,减少绝对值平均体转角,缩短四肢步行周期、支撑时长与摆动时长,缩短四肢制动时长、推进时长。 大鼠造模后 14 d,逐瘀通脉 200 mg / kg 剂量具有增强大鼠皮层梗死周围区 Nestin 蛋白的表达趋势,但各剂量对大鼠血管内皮生长因子(VEGF)和 TNF-α、突触素( SYP)含量没有明显影响。 结论 逐瘀通脉能够显著促进大脑中动脉阻塞脑缺血大鼠肢体运动功能的恢复,其作用机制可能与增强皮层脑梗死周围区 Nestin 蛋白、增加血清 VEGF 以及减少血清 IL-1β 趋势有关,从而减少大脑的神经细胞损伤、促进其发生。

关键词: 逐瘀通脉胶囊, 动脉阻塞, 脑缺血再灌注, 运动功能障碍