目的 探讨caspase-3抑制剂联合钙离子拮抗剂对大鼠脑缺血后神经功能恢复的影响.方法 利用Longa线栓法制备大鼠脑缺血再灌注模型.实验分为生理盐水对照组、caspase-3抑制剂组、尼莫地平组和caspase-3抑制剂联合尼莫地平组(联合用药组).利用Bederson法评价神经功能缺失,采用TUNEL染色和梗死面积评价神经细胞损害.结果 caspase-3抑制剂组、尼莫地平组和联合用药组与对照组相比均可显著改善神经功能缺失.联合用药组与尼莫地平组、对照组相比,TUNEL阳性细胞数明显减少.联合用药组、caspase-3抑制剂组和尼莫地平组与对照组相比,视交叉冠状面的梗死面积均明显减少(P<0.01);联合用药组与尼莫地平组相比,梗死面积亦明显减少.结论 在脑缺血再灌注情况下,联合caspase-3抑制剂和钙离子拮抗剂具有明显的神经保护作用.
Objective To explore the efficacy of combined caspase-3 inhibitor Ac-DEVD-CHO (CASI)and calcium antagonist nimodipine on neurological function recovery after focal cerebral ischemia and reperfusion (I/R) in rats. Methods The cerebral I/R rat made by Longa thread occlusion method were divided into normal saline, CASI, nimodipine and CASI and nimodipine combination group. The neurological function deficit was evaluated by Bederson method, the neurocyte injury was tested by TUNEL and infarct area. Results Neuro- logical function deficit was significantly ameliorated and infarct area of commissura optica coronal plane was obviously decreased (P 〈 0.01 ) in CASI, nimodipine and combination group comparing with those in control group. TUNEL positive cells were significantly decreased in combi- nation group comparing with that in nimodipine and control group. The infarct area of combination group was significantly reduced than that of control group. Conclusions Combined CASI and nimodipine may play pronounced synergistic nettroprotection role in focal cerebral I/R.