神經(jīng)損傷嚴(yán)重影響人類健康。中國(guó)科學(xué)院遺傳發(fā)育所戴建武實(shí)驗(yàn)室與大連醫(yī)科大學(xué)腦疾病研究所合作,，在周圍神經(jīng)損傷后的再生研究中取得了重要進(jìn)展,。
神經(jīng)細(xì)胞外基質(zhì)中富含層粘連蛋白,，在神經(jīng)受到損傷時(shí)，受損部位的層粘連蛋白表達(dá)量升高,。戴建武實(shí)驗(yàn)室研制了能特異與層粘連蛋白結(jié)合的基因工程重組人神經(jīng)生長(zhǎng)因子（LBD-NGF），提出了將神經(jīng)受損部位的內(nèi)源的層粘連蛋白同時(shí)作為L(zhǎng)BD-NGF的結(jié)合靶點(diǎn)和神經(jīng)再生的支架的科研思路,。這一思路不久前在用與膠原特異結(jié)合的VEGF治療心肌損傷中顯示出優(yōu)越性（Zhang et al, Circulation 2009）,。
他們與合作者在大鼠坐骨神經(jīng)鈍挫傷模型中證明，神經(jīng)受損部位的層粘連蛋白能夠作為L(zhǎng)BD-NGF的有效靶點(diǎn),。通過(guò)多種坐骨神經(jīng)功能測(cè)試和組織學(xué)分析表明,，LBD-NGF可以有效地促進(jìn)坐骨神經(jīng)的再生和功能恢復(fù)。戴建武研究員表示該實(shí)驗(yàn)是神經(jīng)損傷修復(fù)研究長(zhǎng)期目標(biāo)的一個(gè)初步嘗試,。在外周神經(jīng)大段缺失損傷修復(fù)時(shí)可能還需要支架材料,。此外，LBD-NGF和生物材料及干細(xì)胞的聯(lián)合使用是否更有利于神經(jīng)損傷的修復(fù),，還需要進(jìn)一步探索,。這項(xiàng)成果為臨床上神經(jīng)損傷的治療提供了新的思路。
這項(xiàng)工作以該實(shí)驗(yàn)室博士研究生孫文杰為第一作者發(fā)表在PLoS ONE上,。該研究受中國(guó)科學(xué)院創(chuàng)新方向項(xiàng)目資助,。（生物谷Bioon.com）
生物谷推薦原始出處：
PLoS ONE 4(7): e6180. doi:10.1371/journal.pone.0006180
Improvement of Sciatic Nerve Regeneration Using Laminin-Binding Human NGF-β
Wenjie Sun1,2, Changkai Sun3, Hui Zhao3, Hang Lin1, Qianqian Han1, Jingyu Wang4, Hui Ma5, Bing Chen1, Zhifeng Xiao1, Jianwu Dai1*
1 Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China, 2 Graduate School, Chinese Academy of Sciences, Beijing, China, 3 Institute of Brain Disorders and the Key Lab for Brain Disorders of Liaoning Province, Dalian Medical University, Dalian, China, 4 Experimental Animal Center of Dalian Medical University, Dalian, China, 5 Department of Pharmaceutics, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
Background
Sciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which finally result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF) plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA), NGF-β could target to nerve cells and improve nerve regeneration.
Methods
Laminin-binding assay and sustained release assay of NGF-β fused with NtA (LBD-NGF) from laminin in vitro were carried out. The bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat sciatic nerve crush injury model, the nerve repair and functional restoration by utilizing LBD-NGF were tested.
Findings
LBD-NGF could specifically bind to laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that LBD-NGF could be retained and concentrated at the nerve injury sites to promote nerve repair and enhance functional restoration following nerve damages.
Conclusion
Fused with NtA, NGF-β could bind to laminin specifically. Since laminin is the major component of nerve extracellular matrix, laminin binding NGF could target to nerve cells and improve the repair of peripheral nerve injuries.
