TAT-mediated delivery of neuroglobin protects against focal cerebral ischemia in mice
TAT-mediated delivery of neuroglobin protects against focal cerebral ischemia in mice
复制标题
TAT 介导的神经球蛋白递送可预防小鼠局灶性脑缺血
DOI：
10.1016/j.expneurol.2010.11.009
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发表时间：
2011-01-01
影响因子：
5.3
通讯作者：
Wu, Zhi-Ying
中科院分区：
文献类型：
--
作者：
Cai, Bin;Lin, Yi;Wu, Zhi-Ying
脑红蛋白（Neuroglobin，Ngb）是一种新发现的脊椎动物脑内珠蛋白，具有保护脑缺氧缺血损伤的作用。然而，由于其体积大，血脑屏障（BBB）对Ngb的不可渗透性限制了其在脑损伤中的应用。最近，11个氨基酸的人免疫缺陷病毒转录反式激活因子（达特）蛋白转导结构域被证明可以成功地将大分子递送到大脑中。本研究旨在探讨TAT-Ngb融合蛋白是否能穿过血脑屏障，对脑缺血有保护作用。免疫组化和Western blotting结果表明，大肠杆菌BL 21（DE 3）表达的TAT-Ngb融合蛋白经静脉注射后可有效地进入小鼠脑组织。两组小鼠分别行大脑中动脉阻塞（MCAO）30 min或2 h后再灌注。各组再分为亚组，分别于MCAO前或再灌注后即刻静脉注射TAT-Ngb、Ngb或生理盐水。与Ngb和生理盐水治疗组相比，MCAO前2小时TAT-Ngb治疗组显示脑梗死体积明显减少，神经功能结局更好（p
Neuroglobin (Ngb), a newly identified globin in vertebrate brain, has been suggested to be able to protect against brain hypoxic-ischemic injury. However, owing to its large size, the impermeability of the blood-brain barrier (BBB) to Ngb limits its application in brain injury. Recently, the 11-amino-acid human immunodeficiency virus trans-activator of transcription (TAT) protein transduction domain was shown to successfully deliver macromolecules into the brain. This study explored whether the TAT-Ngb fusion protein can cross the BBB and protect the brain from cerebral ischemia. The TAT-Ngb fusion protein generated from Escherichia coli BL21 (DE3) was efficiently delivered into mice brain tissues by intravenous injection as demonstrated by immunohistochemistry and Western blotting. Two groups of mice were treated with filamentous middle cerebral artery occlusion (MCAO) for 30 min or 2 h followed by reperfusion. Each group was then divided into sub-groups and was injected intravenously with TAT-Ngb, Ngb, or saline respectively before MCAO or immediately after reperfusion. Compared with the Ngb- and saline-treated group, the group with TAT-Ngb treated 2 h before MCAO showed significantly less brain infarct volume and had better neurologic outcomes (p