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半胱氨酸蛋白酶抑制剂对大鼠脑缺血模型DNA损伤的实验研究 被引量:93

Neuroprotective effects of caspase-3or/and calpain inhibitor on DNA damage in rats subjected to transient focal cerebral ischemia
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摘要 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。 Aim To study the neuroprotective effect s of caspase-3in-hibitorⅢAc-DEVD-CMK or calpain inhibitor ALLN on DNA damage in rats subjected to transient focal cerebr al ischemia.Methods Rats were random-ized to receive intracerebraventricle injection of Ac-DEVD-CMK,ALLN,or both,or vector DMSO,and then were in duced to ischemia by 2hours of left MCA occlusion,followed by 24or 48hours of recirculation.The DNA damage in brain sections was detecte d.Results Pretreatments with cas-pase-3or calpain inhibitor decreased the DNA damage in the ipsilateral brain after transient focal ischemia,in a synergic manner.Conclusion Both caspase-3and calpain might play an i mportant role in ischemic brain dam-age,and the use of specific caspase-3or /and calpain inhibitors might be of potential therapeutic utility in is chemic injuries to the human brain.
出处 《中国临床康复》 CSCD 2003年第7期1064-1065,共2页 Chinese Journal of Clinical Rehabilitation
关键词 实验 半胱氨酸蛋白酶抑制剂 大鼠 脑缺血 DNA损伤 动物模型 cerebral ischemia models,animal enzyme inhibitors DNA damage
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