不同类型神经保护药单独和联合应用对大鼠局灶性脑缺血后神经元凋亡的影响

目的探讨多种不同药理学机制的神经保护药联合应用是否较单独应用对大鼠局灶性脑缺血有更好的保护作用。方法采用线栓法制作大鼠大脑中动脉闭塞模型,分别应用尼莫地平(1mg/kg,n=10)、硫酸镁(100mg/kg,n=10)、MK-801(1mg/kg,n=10)、还原型谷胱甘肽(1g/kg,n=10)、环磷酰胺(63mg/kg,n=10)单独或联合腹腔注射,缺血后6h和24h进行神经功能评价,并观察神经元凋亡和抗凋亡蛋白Bcl-2表达的变化。结果缺血后6h和24h时,联合处理组的神经元凋亡数量显著减少,Bcl-2表达明显增加,与各单药处理组相比有显著差异(P<0·05)。结论神经保护药联合应用对脑缺血的保护作用明显优于单药处理。

The Effect of Various Types of Neuroprotectant Alone and Combined on Neuronal Apoptosis After Focal Cerebral Ischemia in Rats

Objective: To explore whether the combination of various types of neuroprotectants has better protective effect than neuroprotectant alone in focal cerebral ischemia in rats. Methods: A rat middle cerebral artery occlusion model was made by insertion of a thin nylon thread. Nimodipine (1 mg/kg, n=10), magnesium sulfate (100 mg/kg, n=10), MK-801(1 mg/kg, n=10), Reduced glutathione (1 g/kg, n=10), cyclophosphamide (63 mg/kg, n=10) were administered alone or in combination for intraperitoneal injection. The neurological function was evaluated at 6 and 24 hours after the focal cerebral ischemia. The changes of the expressions of neuronal apoptosis and anti-apoptosis protein Bcl-2 were observed. Results: The numbers of neuronal apoptosis decreased significantly in the combined treatment group, and the expression of Bcl-2 increased significantly, and there were significant differences among the groups treated with one neuroprotectant (P<0.05). Conclusion: The cerebral ischemic protection of the combination of neuroprotectants was remarkably superior to neuroprotectant alone.