第四军医大学徐礼鲜教授课题组和西安医学院苟兴春博士课题组的研究人员研制了一种有效穿过血脑屏障靶向缺血区的蛋白质药物,这对于脑缺血损伤相关疾病的治疗具有重要意义。
这一研究成果公布在《Biomaterials》杂志上。主持这一研究的是第四军医大学徐礼鲜教授和西安医学院苟兴春博士。苟兴春博士毕业于第四军医大学,并在徐礼鲜教授指导下从事博士后研究工作,在脑血管保护和神经再生研究方面获得多项成果。
脑卒中(Stroke)是脑中风的学名,是一种突然起病的脑血液循环障碍性疾病。是指在脑血管疾病的病人,因各种诱发因素引起脑内动脉狭窄,闭塞或破裂,而造成急性脑血液循环障碍,临床上表现为一过性或永久性脑功能障碍的症状和体征.脑卒中分为缺血性脑卒中和出血性脑卒中。
据统计我国每年发生脑中风病人达200万。发病率高达120/10万。现幸存中风病人700万,其中450万病人不同程度丧失劳动力和生活不能自理。致残率高达75%。我国每年中风病人死亡120万。已得过脑中风的患者,还易再复发,每复发一次,加重一次。所以,更需要采取有效措施预防复发。
在这篇题为“靶向Ngn2蛋白治疗脑缺血损伤”(Targeted delivery of Neurogenin-2 protein in the treatment for cerebral ischemia-reperfusion injury)的文章中,研究人员通过蛋白重组技术将TAT(蛋白转导结构域)、LBD(Laminin banding dowmain)和Ngn2融合表达,得到了一种可以穿过血脑屏障并靶向缺血区从而发挥脑保护作用,而且副作用较小。
生物谷推荐英文摘要:
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.