Nonviral HVJ (hemagglutinating virus of Japan) liposome-mediated retrograde gene transfer of human hepatocyte growth factor into rat nervous system promotes functional and histological recovery of the crushed nerve

Nonviral HVJ (hemagglutinating virus of Japan) liposome-mediated retrograde gene transfer of human hepatocyte growth factor into rat nervous system promotes functional and histological recovery of the crushed nerve
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DOI:
10.1016/j.neures.2005.04.004
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发表时间:
2005-08-01
影响因子:
2.9
通讯作者:
Fujikawa, K
Fujikawa, K
中科院分区:
医学4区
文献类型:
--
作者:
Kato, N;Nemoto, K;Fujikawa, K

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众所周知,肝细胞生长因子(HGF)参与许多生物功能,例如器官再生和血管生成,并对运动神经元、感觉神经元和副交感神经元发挥神经营养作用。在本研究中,我们采用非病毒HVJ(日本血凝病毒)脂质体方法,重复肌肉注射人HGF基因,以检测该基因转染大鼠神经系统是否能够发挥神经营养作用,促进受损神经的恢复。 HGF 蛋白和 HGF mRNA 的表达表明基因转移到神经系统确实是通过逆行轴突转运发生的。挤压后 4 周,挤压神经的电生理检查显示,重复注射 HGF 基因后,平均潜伏期显着缩短,平均最大 M 波振幅显着增大。此外,组织学结果显示,重复注射HGF基因组的轴突平均直径、轴突数量和轴突数量显着更大。上述结果表明,将人HGF基因重复转移到大鼠神经系统中能够在电生理学和组织学上促进受压神经的恢复,并表明HGF基因转移具有治疗受压神经的潜力。 (c) 2005 年爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
Hepatocyte growth factor (HGF) is well known to be involved in many biological functions, such as organ regeneration and angiogenesis, and to exert neurotrophic effects on motor, sensory, and parasympathetic neurons. In this study, we gave repeated intramuscular injections of the human HGF gene, using nonviral HVJ (hemagglutinating virus of Japan) liposome method, to examine whether transfection of the rat nervous system with this gene is able to exert neurotrophic effects facilitating recovery of a crushed nerve. The expression of HGF protein and HGF mRNA indicated that gene transfer into the nervous system did occur via retrograde axonal transport. At 4 weeks after crush, electrophysiological examination of the crushed nerve showed a significantly shorter mean latency and a significantly greater mean maximum M-wave amplitude with repeated injections of HGF gene. Furthermore, histological findings showed that the mean diameter of the axons, the axon number and the axon population were significantly larger in the group with repeated injections of HGF gene. The above results show that repeated human HGF gene transfer into the rat nervous system is able to promote crushed-nerve recovery, both electrophysiotogically and histologically, and suggest that HGF gene transfer has potential for the treatment of crushed nerve. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.