Src family kinase-inhibitor PP2 reduces focal ischemic brain injury

Src family kinase-inhibitor PP2 reduces focal ischemic brain injury
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DOI:
10.1111/j.1600-0404.2004.00306.x
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发表时间:
2004-09-01
影响因子:
3.5
通讯作者:
Terént, A
Terént, A
中科院分区:
医学3区
文献类型:
--
作者:
Lennmyr, F;Ericsson, A;Terént, A

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目的:研究Src家族激酶(SFK)抑制剂4-氨基-5-(4-氯苯基)-7-(t-丁基)吡唑啉(3,4-d)嘧啶(PP2)对大鼠短暂性局灶性脑缺血的神经保护作用。材料与方法:Sprague-Dawley大鼠短暂性(90 min)大脑中动脉闭塞(MCAO), 1天后评估存活情况。MCAO后30 min给予PP2 (1.5 mg/kg i.p.)或载药。病变采用磁共振成像(MRI)、三苯基氯化四氮唑(TTC)染色检查,并根据Bederson等人的方法采用神经学评分法确定功能结局。结果:与对照组相比,pp2治疗大鼠的t2加权MRI和TTC染色显示梗死面积缩小约50% (P < 0.05)。PP2组神经功能评分明显高于对照组(P < 0.05)。结论- PP2是一种潜在的脑缺血再灌注神经保护剂。PP2对SFKs和/或其他途径的干扰仍有待阐明。
Objectives - To investigate the neuroprotective potential of the Src family kinase (SFK) inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo(3,4-d)pyrimidine (PP2) in transient focal cerebral ischemia in the rat. Material and methods - Sprague-Dawley rats were exposed to transient (90 min) middle cerebral artery occlusion (MCAO) and evaluated after 1 day of survival. PP2 (1.5 mg/kg i.p.) or vehicle was given 30 min after MCAO. The lesions were examined with magnetic resonance imaging (MRI), tri-phenyl tetrazolium chloride (TTC) staining and the functional outcome was determined using neurological scoring according to Bederson et al. Results - PP2-treated rats showed approximately 50% reduction of infarct size on T2-weighted MRI and in TTC staining compared with controls (P < 0.05). Moreover, the neurological score was better in the PP2 group than controls (P < 0.05). Conclusion - PP2 is a potential neuroprotective agent in cerebral ischemia-reperfusion. The interference of PP2 with SFKs and/or other pathways remains to be elucidated.