钙蛋白酶抑制剂减少大鼠局灶性脑缺血再灌注模型海马CA1区神经元凋亡

Effect of Calpain Inhibitor in Reducing Neuron Apoptosis of Hippocampal CA1 Section of the Focal Cerebral Ischemia-Reperfusion Model in Rats

目的:研究钙蛋白酶抑制剂calpeptin干预治疗对大鼠局灶性脑缺血再灌注模型海马CA1区神经元凋亡的影响及其可能机制。方法:选择健康成年雄性SD大鼠128只作为研究动物,采用随机数字表法将其分为MACO组、calpeptin组、DMSO组及sham组,制作大鼠左侧大脑中动脉缺血再灌注模型,缺血2 h后分别再灌注6、12、24 h及48 h后进行神经功能学评分,免疫组化检测海马CA1区神经元caspase-3的表达,TUNEL法检测原位细胞凋亡,观察海马CA1区神经元凋亡。结果:DMSO组的各项检测指标与MACO组比较差异无统计学意义(P>0.05);calpeptin组的神经功能评分及caspase-3表达均低于同时间点MCAO组及DMSO组,比较差异均有统计学意义(P<0.05);再灌注12、24、48 h后,calpeptin组神经元凋亡情况优于同时间点MCAO组及DMSO组,比较差异均有统计学意义(P<0.05)。结论:calpeptin可减少大鼠局灶性脑缺血再灌注模型海马CA1区的神经元凋亡,对脑缺血再灌注损伤有保护作用,其机制可能与抑制caspase-3的表达有关。

Objective：To study the influence and mechanism of calpain inhibitor calpeptin in neuron apoptosis of hippocampal CA1 section in rats with focal cerebral ischemia-reperfusion.Method：128 health adult male SD rates were selected as the research animals.They were divided into the MACO group,the calpeptin group,the DMSO group and the sham group.The left middle cerebral artery（MCA） occlusion model was performed.2 hours after the left middle cerebral artery occlusion,recirculations of 6,12,24 hours and 48 hours were given to the rates.6,12,24 hours and 48 hours after the recirculations,the neurological functions of the rats were evaluated,immunohistochemistry was used to detect the expression of caspase-3 in hippocampal CA1 section and the neuronal apoptosis in hippocampal CA1 section was detected by the method of terminal deoxynucleotidyl transferase（Td T）-mediated d UTP nick end-labelling（TUNEL）.Result：The differences in the indexes between the MCAO group and the MACO group were not statistically significant（P〉0.05）.The scores of neurological functions and the expression of caspase-3 in the calpeptin group were lower than those in the MCAO group and the MACO group,the differences were statistically significant（P〈0.05）.12,24 hours and 48 hours after the recirculations,the situations of neuronal apoptosis in the calpeptin group were better than those in the MCAO group and the MACO group,the differences were statistically significant（P〈0.05）.Conclusion：Calpeptin can reduce the neuronal apoptosis of hippocampal CA1 section in rats with ischemia-reperfusion injury and the mechanism may be related to the inhibition of the expression of caspase-3.