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目的 :研究半胱氨酸蛋白酶caspase 3及calpain抑制剂干预治疗对大鼠局灶性脑缺血 /再灌注模型caspase 3表达的影响。方法 :大鼠随机分为经左侧侧脑室注射caspase 3抑制剂Ⅲ组 (DEVD组 )、calpain抑制剂Ⅰ组 (ALLN组 )、联合治疗组 (DEVD +ALLN组 )、溶剂二甲基亚砜对照组 (DMSO组 )以及左侧大脑中动脉缺血 /再灌注对照组 (MCAO组 ) ,诱导左侧大脑中动脉缺血 2h ,再灌注2 4或 48h ;再灌注 2 4h进行TTC染色观察梗死灶的形成情况 ;用TdT介导的dUTP缺口末端标记技术 (TUNEL)检测鼠脑中的神经元凋亡情况 ;并分别通过原位杂交和免疫组化技术检测鼠脑中caspase 3mRNA及活性蛋白的表达。结果 :DMSO组的各项指标与MCAO组无明显差异 ;DEVD组或ALLN组缺血侧脑中细胞凋亡数、caspase 3mRNA及活性蛋白的表达均明显减少 ,联合治疗组作用更强。结论 :caspase 3与calpain抑制剂干预治疗可减少大鼠缺血再灌注脑区神经元凋亡和caspase 3的表达 ,从而产生神经保护作用 ,并具有潜在的临床应用价值。
Objective: To investigate the effects of caspase 3 and calpain inhibitor on the expression of caspase 3 in rat focal cerebral ischemia / reperfusion model. Methods: The rats were randomly divided into 3 groups: the DEVD group, the calpain inhibitor group Ⅰ (ALLN group), the DEVD + ALLN group, the solvent dimethylsulfoxide Control group (DMSO group) and left middle cerebral artery ischemia / reperfusion control group (MCAO group), induced left middle cerebral artery ischemia 2h, reperfusion 24 or 48h; reperfusion 24hours TTC staining infarction TdT-mediated dUTP nick end labeling (TUNEL) was used to detect neuronal apoptosis in the rat brain. Caspase 3 mRNA and protein were detected by in situ hybridization and immunohistochemistry expression. Results: There was no significant difference between DMSO group and MCAO group. The number of apoptotic cells, the expression of caspase 3 mRNA and active protein in the ischemic brain of DEVD group or ALLN group were significantly decreased, and the combined treatment group was more effective. Conclusion: The intervention of caspase 3 and calpain inhibitor can reduce the neuronal apoptosis and the expression of caspase 3 in the brain after ischemia-reperfusion in rats, and thus have neuroprotection and have potential clinical value.