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目的研究caspase-3抑制剂Ac-DEVD-CMK及calpain抑制剂ALLN干预治疗对大鼠局灶性脑缺血/再灌注模型的神经保护作用。方法经左侧侧脑室注射DEVD或/和ALLN及溶剂二甲基亚砜(DMSO)后,制作大鼠左侧MCA缺血再灌注模型;缺血2h再灌注24h进行TTC染色观察梗死灶的形成情况;并分别于缺血2h再灌注24h或48h检测鼠脑中单、双链DNA断裂情况。结果溶剂DMSO预处理组的各项指标与MCAO模型组无明显差异;DEVD或ALLN治疗后缺血侧脑中Klenow及TUNEL阳性细胞数均明显减少,二者合用作用最强。结论Caspase-3与calpain均在缺血性脑损伤中起重要作用,对此进行治疗干预具有潜在的临床应用价值。
Objective To investigate the neuroprotective effect of Ac-DEVD-CMK inhibitor caspase-3 and ALLN inhibitor calpain inhibitor on focal cerebral ischemia / reperfusion in rats. Methods The left MCA model of ischemia-reperfusion injury was induced by injecting DEVD or / and ALLN and DMSO in the left lateral ventricle. TTC staining was used to observe the formation of infarction The DNA fragmentation of single and double stranded DNA in rat brain was detected at 24h or 48h after reperfusion for 2h after ischemia respectively. Results The indexes of solvent DMSO pretreatment group had no significant difference with MCAO model group. The numbers of Klenow and TUNEL positive cells in ischemic brain decreased significantly after DEVD or ALLN treatment, and the combination of them was the strongest. Conclusions Both Caspase-3 and calpain play an important role in ischemic brain injury. It is potentially of clinical value for therapeutic intervention.