第四軍醫(yī)大學(xué)徐禮鮮教授課題組和西安醫(yī)學(xué)院茍興春博士課題組的研究人員研制了一種有效穿過血腦屏障靶向缺血區(qū)的蛋白質(zhì)藥物，這對(duì)于腦缺血損傷相關(guān)疾病的治療具有重要意義,。
這一研究成果公布在《Biomaterials》雜志上,。主持這一研究的是第四軍醫(yī)大學(xué)徐禮鮮教授和西安醫(yī)學(xué)院茍興春博士。茍興春博士畢業(yè)于第四軍醫(yī)大學(xué),，并在徐禮鮮教授指導(dǎo)下從事博士后研究工作,，在腦血管保護(hù)和神經(jīng)再生研究方面獲得多項(xiàng)成果,。
腦卒中（Stroke）是腦中風(fēng)的學(xué)名，是一種突然起病的腦血液循環(huán)障礙性疾病,。是指在腦血管疾病的病人,，因各種誘發(fā)因素引起腦內(nèi)動(dòng)脈狹窄，閉塞或破裂,，而造成急性腦血液循環(huán)障礙,，臨床上表現(xiàn)為一過性或永久性腦功能障礙的癥狀和體征．腦卒中分為缺血性腦卒中和出血性腦卒中。
據(jù)統(tǒng)計(jì)我國每年發(fā)生腦中風(fēng)病人達(dá)200萬,。發(fā)病率高達(dá)120/10萬。現(xiàn)幸存中風(fēng)病人700萬,，其中450萬病人不同程度喪失勞動(dòng)力和生活不能自理,。致殘率高達(dá)75%。我國每年中風(fēng)病人死亡120萬,。已得過腦中風(fēng)的患者,，還易再復(fù)發(fā)，每復(fù)發(fā)一次,，加重一次,。所以，更需要采取有效措施預(yù)防復(fù)發(fā),。
在這篇題為“靶向Ngn2蛋白治療腦缺血損傷”（Targeted delivery of Neurogenin-2 protein in the treatment for cerebral ischemia-reperfusion injury）的文章中,，研究人員通過蛋白重組技術(shù)將TAT（蛋白轉(zhuǎn)導(dǎo)結(jié)構(gòu)域）、LBD（Laminin banding dowmain）和Ngn2融合表達(dá),，得到了一種可以穿過血腦屏障并靶向缺血區(qū)從而發(fā)揮腦保護(hù)作用,，而且副作用較小。
生物谷推薦英文摘要：
Biomaterials doi: 10.1016/j.biomaterials
Targeted delivery of Neurogenin-2 protein in the treatment for cerebral ischemia-reperfusion injury.
Deng B, Gou X, Chen H, Li L, Zhong H, Xu H, Jiang F, Zhao Z, Wang Q, Xu L.
Abstract
Neurogenin-2 (Ngn2), as a proneural gene that promotes the survival and differentiation of neural precursor cells, is an attractive candidate for therapy against cerebral ischemia-reperfusion injury. However, the delivery approach limits its clinical application. To deliver Ngn2 protein into the cerebral ischemic region and exert a therapeutic effect on injured neurons after ischemia, we here reported that the fusion protein TAT-LBD-Ngn2 was constructed by fusing a transactivator of transcription (TAT) domain and a laminin-binding domain (LBD) to Ngn2. TAT-LBD-Ngn2 promoted the outgrowth of neuronal neurite, increased the survival rate and alleviated apoptosis of hippocampal neurons exposed to oxygen glucose deprivation in vitro. Furthermore, a focal cerebral ischemia model in C57BL/6 mice showed that TAT-LBD-Ngn2 efficiently crossed the blood brain barrier, aggregated in the ischemic zone and was consistently incorporated into neurons. Moreover, TAT-LBD-Ngn2 transduced into brains attenuated neuronal degeneration and apoptosis in the ischemic zone. TAT-LBD-Ngn2 treatment resulted in a reduction of infarct volume that was associated with a parallel improvement in neurological functional outcomes after reperfusion. In conclusion, the targeted delivery of TAT-LBD-Ngn2 into the ischemic zone attenuated cerebral ischemia-reperfusion injury through the inhibition of neuronal degeneration and apoptosis, suggesting that TAT-LBD-Ngn2 is a promising target candidate for the treatment of ischemic stroke.
