BMP7 reduces synergistic injury induced by methamphetamine and ischemia in mouse brain

BMP7 reduces synergistic injury induced by methamphetamine and ischemia in mouse brain
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DOI:
10.1016/j.neulet.2008.06.052
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发表时间:
2008-09-05
影响因子:
2.5
通讯作者:
Wang, Yun
Wang, Yun
中科院分区:
医学4区
文献类型:
--
作者:
Shen, Hui;Luo, Yu;Wang, Yun

文献摘要

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以往的研究表明,甲基苯丙胺(MA)增强脑缺血引起的神经退行性变。我们和其他人已经报道了骨形态发生蛋白7 (BMP7)对MA和缺血性脑损伤具有保护作用。本研究的目的是研究BMP7是否能减少MA和脑缺血引起的协同损伤。成年CD-1小鼠分别用MA (4 × 10 mg/kg,每次间隔2 h)或生理盐水处理。通过定量实时聚合酶链反应,我们发现MA在注射后1天抑制大脑皮层BMP7 mRNA的表达。注射MA后90 min,结扎右侧大脑中动脉进行缺血和再灌注损伤。分别于再灌注后1 h和2 d处死动物进行caspase-3/7活性测定和三苯基氯化四氮唑染色。MA预处理后脑卒中大鼠脑梗死及caspase-3/7活性增强;用BMP7预处理后,两种反应均减弱。总之,我们的数据表明,MA促进脑缺血后脑梗死可能部分通过抑制BMP7介导。爱思唯尔爱尔兰有限公司出版。
Previous studies have indicated that methamphetamine (MA) potentiates neurodegeneration induced by ischemia in brain. We, and others, have reported that bone morphogenetic protein 7 (BMP7) is protective against MA and ischemic brain injury. The purpose of this study is to examine whether BMP7 reduces synergistic injury induced by both MA and cerebral ischemia. Adult CD-1 mice were treated with MA (4 x 10 mg/kg, each dose 2 h apart) or saline. Using the quantitative real time polymerase chain reaction, we found that MA suppressed the expression of BMP7 mRNA in the cerebral cortex 1 day after injection. Ischemic and reperfusional injuries were introduced by ligation of the right middle cerebral artery for 90 min after MA injection. Animals were sacrificed for caspase-3/7 activity assay and tri-phenyl-tetrazolium chloride staining at I h and 2 days after reperfusion, respectively. Cerebral infarction and caspase-3/7 activity were enhanced in the stroke animals pretreated with MA; both responses were attenuated by pretreatment with BMP7. In conclusion, our data suggest that MA facilitates cerebral infarction after ischemia possibly mediated, in part, through the suppression of BMP7. Published by Elsevier Ireland Ltd.