CAJ | 학술논문

目的观察脑缺血再灌注损伤后Cuspuse-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3 h Cuspuse-3活性即开始升高,并随着时间的延长而进一步升高,12～24 h达到高峰;(2)脑缺血再灌注损伤后24 h Cuspuse-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)mm3和(21.6±4.9)mm3,两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Cuspase-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.
목적 관찰뇌결혈재관주손상후Cuspuse-3격활재신경원세포조망중적작용이급Z-DEVD.fmk대결혈재관주손상적보호작용.방법 채용MACo법건립소서급성뇌결혈모형,이매활성측정、Western잡교등방법대Caspase-3활성변화화격활진행규률성관찰;통과뇌실내주사급여Z-DEVD.fmk,관찰기대Caspase-3격활적영향급기대뇌결혈재관주손상적보호작용.결과 (1)뇌결혈재관주손상후3 h Cuspuse-3활성즉개시승고,병수착시간적연장이진일보승고,12～24 h체도고봉;(2)뇌결혈재관주손상후24 h Cuspuse-3명현격활,고우가수술조7.6배(P<0.01);(3)여DMSO대조조비교,Z-DEVD.fmk치료조Caspase-3격활명현강저(P<0.01);(4)DMSO대조조화Z-DEVD.fmk치료조뇌결혈체적분별위(40.9±4.1)mm3화(21.6±4.9)mm3,량조비교차이유통계학의의(P<0.01);이차신경공능평분Z-DEVD.fmk치료조(0.8±0.4)명현저우DMSO대조조(2.2±0.3,P<0.05).결론 뇌결혈재관주손상후조기Caspase-3명현격활,뇌실내주사Z-DEVD.fmk대Cuspase-3격활유명현억제작용,대뇌결혈재관주손상기보호작용,유조우아문진일보연구뇌결혈재관주손상적궤제.
Objective To evaluate the effects of Caspase-3 activation and neuroprotection of ZDEVD. fmk in cerebral ischemia repeffusion 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 repeffusion. Caspase-3 activation ,infarct volume and neurological score were measured and evaluated after intraventricular injection of Z-DEVD. fmk. Results (1) Caspase-3 activation occurred 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 ) mm3 ] was significantly less than that in DMSO control group [ (21.6 ± 4.9) mm3, P < 0.01 ]. Neurological score in ZDEVD. 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.