中文摘要：

目的观察脑缺血再灌注损伤后Caspase-3激活在神经元细胞凋亡中的作用以及Z-DEVD．fmk对缺血再灌注损伤的保护作用。方法采用MACo法建立小鼠急性脑缺血模型，以酶活性测定、Western杂交等方法对Caspase-3活性变化和激活进行规律性观察；通过脑室内注射给予Z-DEVD．fmk，观察其对Caspase-3激活的影响及其对脑缺血再灌注损伤的保护作用。结果（1）脑缺血再灌注损伤后3h Caspase-3活性即开始升高，并随着时间的延长而进一步升高，12～24h达到高峰；（2）脑缺血再灌注损伤后24h Caspase-3明显激活，高于假手术组7．6倍（P〈0．01）；（3）与DMSO对照组比较，Z-DEVD．fmk治疗组Caspase-3激活明显降低（P〈0．01）；（4）DMSO对照组和Z-DEVD．fmk治疗组脑缺血体积分别为（40．9±4．1）mm^3和（21．6±4．9）mm^3，两组比较差异有统计学意义（P〈0．01）；而且神经功能评分Z-DEVD．fmk治疗组（0．8±0．4）明显低于DMSO对照组（2．2±0.3，P〈0．05）。结论脑缺血再灌注损伤后早期Caspase-3明显激活，脑室内注射Z-DEVD．fmk对Caspase-3激活有明显抑制作用，对脑缺血再灌注损伤起保护作用，有助于我们进一步研究脑缺血再灌注损伤的机制。

英文摘要：

Objective To evaluate the effects of Caspase-3 activation and neuroprotection of Z- DEVD. fmk in cerebral ischemia reperfusion induced neuronal cell death. Methods Focal cerebral ischemia C57L mice model was established by middle cerebral occlusion （MACo） method. Caspase-3 activity and activation was determined by enzyme activity assay and Western blot at different time points after completion of ischemia reperfusion. Caspase-3 activation,infarct volume and neurological score were measured and evaluated after intraventricular injection of Z-DEVD. fmk. Results （ 1 ） Caspase-3 activation occrred immediately at 3 h after ischemia reperfusion,gradually increased and reached the peak at 12-24 h. （2） Caspase-3 was significantly activated at 24 h after ischemia reperfusion, and its activation was increased by 7.6 times in comparison with the sham controls （ P 〈 0.01 ）. （ 3 ） As compared with DMSA control group,the Caspase-3 Caspase-3 activation was decreased by 2.5 times in Z-DEVD. fmk treatment group （ P 〈 0.01 ）. （4） Infarct volume in Z-DEVD. fmk treatment group [ （ 40.9 ± 4.1 ） mm^3 ] was significantly less than that in DMSO control group [ （21.6± 4.9） mm^3, P 〈 0.01 ]. Neurological score in Z- DEVD. fmk treatment group （ 0.8 ± 0.4 ） was also significantly less than that in DMSO control group （2.2± 0.3 ,P 〈 0.05 ）. Conclusion Caspase-3 activation plays critical role in neuronal cell death induced by cerebral ischemeia reperfusion. Caspase-3 activation was significantly inhibited by Z-DEVD. fmk via intraventricular injection. Z-DEVD. fmk has dramatic neuroprotective effect in cerebral ischemeia reperfusion injury. It provides insights into the mechanism of events involved in ischmeia reperfusion injury.