【摘要】 目的 研究半胱氨酸蛋白酶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Calpain表达的影响。方法 大鼠随机分为经左侧侧脑室注射Ac-DEVD-CMK(DEVD组)、ALLN(ALLN组)、二者联合(DEVD+ALLN组)或溶剂二甲基亚砜组(DMSO组)，以及缺血对照组(MCAO组)，诱导左侧MCA缺血2h，再灌注24或48h；再灌注24h进行TTC染色观察梗死灶的形成情况；分别通过原位杂交和免疫组化技术检测鼠脑中Calpain mRNA及活性蛋白的表达。结果 DMSO组的各项指标与MCAO组差异无显著性；DEVD组或ALLN组缺血侧脑中Calpain mRNA及活性蛋白的表达均明显减少，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，针对它们进行治疗干预具有潜在的临床应用价值。

    关键词 脑缺血 半胱氨酸蛋白酶 Caspase-3 Calpain 抑制剂 干预

    Effects of cysteine protease inhibitor on calpain expression in rat brains subjected to transient focal cerebral ischemia

    Wang Yuhui,Xia Chunlin,Shao Fuyuan

    Department of Neurology,Pu’nan Hospital of Shanghai,Shanghai 200125.

    【Abstract】 Objective To study the effects of cysteine protease caspase-3 inhibitor Ⅲ Ac-DEVD-CMK or calpain inhibitor ALLN on calpain expression in rat brains subjected to transient focal cerebral ischemia.Methods Rats were randomized to receive intracerebraventricle injection of Ac-DEVD-CMK(group DEVD),ALLN(group ALLN),or both(group DEVD plus ALLN),or vector DMSO(group DMSO),and then were induced to ischemia by 2 hours of left middle cerebral artery occlusion(MCAO),followed by 24 or 48 hours of recirculation.Infarct zones were confirmed by 2,3,5-triphenyltetrazolium chloride(TTC)staining at 24 hours of recirculation,in situ hybridization and immunohistochemistry were performed in rats brain sections to detect calpain expression at the mRNA level,and the active protein level separately.Results Pretreatments with caspase-3 or calpain inhibitor decreased the calpain expression in the ipsilateral brain after transient focal ischemia,in a synergic manner.Conclusion Both caspase-3 and calpain might play an important role in ischemic brain damage ......