Caspase-3抑制剂对蛛网膜下腔出血后早期脑损伤的作用

Effects of Caspase-3 Inhibitor on Early Brain Injury after Subarachnoid Hemorrhage in Rats

目的探讨Caspase-3抑制剂在蛛网膜下腔出血后早期脑损伤中的作用。方法颈内动脉穿刺制作大鼠蛛网膜下腔出血模型。将大鼠随机分成3组:实验组(38只)模型制作后腹腔注射Caspase-3抑制剂Z-VAD-FMK(10μmol/L,0.3 mL);对照组(38只)注射等体积二甲基亚砜(DMSO);正常组(16只)未进行任何处理。72 h记录死亡率、神经功能评分、脑水肿、血脑屏障通透性等脑损伤指标;TUNEL染色检测神经元细胞凋亡,免疫组化、Western Blot检测Caspase-3表达。结果 Caspase-3抑制剂可降低大鼠死亡率(4 7.4%vs2 8.9%,P<0.0 5),减轻脑水肿,保护血脑屏障,减少Caspase-3蛋白表达及神经元细胞凋亡(P<0.05),但对神经功能评分无明显影响(P>0.05)。结论细胞凋亡在SAH后早期脑损伤中起重要作用,可减轻SAH后早期脑损伤。

Objective To explore the effects of cell apoptosis in the early brain injury after subarachnoid hemorrhage（SAH）.Methods The models with SAH were induced through puncturing of the bifurcation of left ICA in male Sprague-Dawley rats.The rats were divided randomly into three groups：Experimental group（n=38） given with Caspase-3 inhibitor（Z-VAD-FMK,10 μmol/L,0.3 mL） just after operation,control group（n=38） injected with equal volume of DMSO,and normal rats（n=16） as negative control.Mortality,neurological scores,brain edema,and permeability of brain-blood barrier（BBB） were recorded at 72 h.Apoptosis of neuronal cells was detected using TUNEL staining.Expression of Caspase-3 in the brain was investigated by Western blot and immunochemistry.Results The Caspase-3 inhibitor decreased the mortality and brain edema,and preserved the permeability of BBB（P0.05）.No obvious difference was observed in neurological scores between the experimental group and control groups（P0.05）.Apoptosis of neuronal cells was decreased significantly in the experimental group（P0.05）.Expression of Caspase-3 was downregulated by Z-VAD-FMK（P0.05）.Conclusion Apoptosis play an important role in the early brain injury after SAH.Inhibition of apoptosis may be an effective method for the treatment of early brain injury after SAH.