目的：探讨奥拉西坦(oxiracetam)对脑梗死大鼠细胞凋亡及神经再生的影响。方法：60只健康成年雄性SD大鼠随机分为假手术组、生理盐水组、奥拉西坦组(n=20/组)。大鼠右侧大脑中动脉阻塞脑缺血模型成功后，生理盐水组给予尾静脉注射无菌生理盐水1 mL，连续14 d；奥拉西坦组尾静脉注射无菌生理盐水配置的奥拉西坦1 mL，注射剂量为200 mg/kg，连续14 d；假手术组仅切开颈部肌肉，暴露颈总动脉后缝合。模型成功后同时给予大鼠腹腔注射BrdU (50 mg/kg)，bid，连续7 d以标记新生细胞。比较各组动物的神经功能评分，用TUNEL荧光标记测定细胞凋亡，BrdU、微管相关蛋白(doublecortin，DCX)免疫荧光技术标记增殖细胞及新生神经元。结果：与假手术组相比，脑梗死(生理盐水组和奥拉西坦组)大鼠的神经功能明显降低(均 P<0.05)；治疗后，奥拉西坦组的大鼠神经功能比生理盐水组明显改善，差异有统计学意义(P<0.05)。脑梗死后，大鼠缺血脑组织的细胞凋亡明显增加，但奥拉西坦组的细胞凋亡明显少于生理盐水组，而增殖细胞及新生神经元显著多于假手术组和生理盐水组(P<0.05)。结论：奥拉西坦可减少细胞凋亡、促进神经再生，从而改善脑梗死大鼠的神经功能。%Objective: To study the effects of oxiracetam on apoptosis and neurogenesis in rat ischemic stroke model. Methods: 60 adult male Sprague Dawley rats were randomly separated into three groups, including sham operation group, saline group, oxiracetam group(n=20/group). Rat right middle cerebral artery transient occlusion(MCAO) model was established. Two separate groups were administered with either oxiracetam or saline via the tail vein immediately after artery occlusion for 14 days . Neck muscles and carotid artery were in sham operation group exposed . And BrdU ( 50 mg/kg ) was performed intraperitoneal injection to all rats twice a day for 7 days to label stem cells. The neural function was compared among the three groups. TUNEL immunofluorescence was used to detect apoptosis , BrdU and DCX immunofluorescence were used to observe neurogenesis in ischemic brain. Results: After MCAO, the neural function in saline group and oxiracetam group obviously decreased(P<0.05) as compared with sham operation group. But the function in oxiracetam group was better than that in saline group after treatment ( P<0 . 05 ) . The number of BrdU and DCX positive cell was significantly higher than those in sham operation group and saline group(P<0.05 respectively), while the TUNEL positive cell in oxiracetam group was less than that in saline group. Conclusion: Oxiracetam may promote neuronal function via reducing apoptosis and stimulating neurogenesis.
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