Stachybotrys microspora triprenyl phenol-7, a novel fibrinolytic agent, suppresses superoxide production, matrix metalloproteinase-9 expression, and thereby attenuates ischemia/reperfusion injury in rat brain
Stachybotrys microspora triprenyl phenol-7, a novel fibrinolytic agent, suppresses superoxide production, matrix metalloproteinase-9 expression, and thereby attenuates ischemia/reperfusion injury in rat brain
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DOI：
10.1016/j.neulet.2011.08.018
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发表时间：
2011-10-03
影响因子：
2.5
通讯作者：
Tominaga, Teiji
中科院分区：
文献类型：
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作者：
Akamatsu, Yosuke;Saito, Atsushi;Tominaga, Teiji
小孢穗柄霉三异戊烯基酚-7（SMTP-7）是一种新型的具有抗炎作用的纤溶药物。先前的研究表明，与组织型纤溶酶原激活剂（tPA）相比，SMTP-7进一步改善了小鼠栓塞性中风模型中的梗死体积，但SMTP-7具有比tPA更有益效果的原因尚未确定。在本研究中，我们研究了SMTP-7是否对短暂性局灶性脑缺血（tFCI）具有内在的神经保护作用。Sprague-Dawley大鼠通过大脑中动脉管腔内闭塞2小时进行tFCI。在诱导tFCI后，基于施用的药剂将大鼠随机分为两组：SMTP-7组和媒介物组。再灌注后24 h检测脑梗死体积，并检测超氧化物产生、硝基酪氨酸和基质金属蛋白酶-9（MMP-9）的表达，这些在继发性脑损伤和出血性转化中起主要作用。结果表明，SMTP-7显著抑制tFCI后超氧化物的产生，硝基酪氨酸和MMP-9的表达，从而减轻缺血性神经元损伤。这些结果表明，SMTP-7通过抑制氧化应激和MMP-9活化对缺血/再灌注损伤具有内在的神经保护作用。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Stachybotrys microspora triprenyl phenol-7 (SMTP-7) is a novel fibrinolytic agent with anti-inflammatory effect. Previous study demonstrated that SMTP-7 further ameliorated infarction volume in a mouse embolic stroke model compared with tissue type plasminogen activator (tPA), but the reason SMTP-7 has more beneficial effect than tPA has not yet been determined. In the present study, we investigated whether SMTP-7 has an intrinsic neuroprotective effect against transient focal cerebral ischemia (tFCI). Sprague-Dawley rats were subjected to tFCI by intraluminal middle cerebral artery occlusion for 2 h. Following induction of tFCI, rats were randomized into two groups based on the agent administered: SMTP-7 group and vehicle group. We examined cerebral infarction volume 24 h after reperfusion, and evaluated superoxide production, the expressions of nitrotyrosine and matrix metalloproteinase-9 (MMP-9), which play major roles in secondary brain injury and hemorrhagic transformation. The findings showed that SMTP-7 significantly suppressed superoxide production, the expression of nitrotyrosine and MMP-9 after tFCI, and consequently attenuated ischemic neuronal damage. These results suggest that SMTP-7 has an intrinsic neuroprotective effect on ischemia/reperfusion injury through the suppression of oxidative stress and MMP-9 activation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.