Kato Naoki, Nemoto Koichi, Nakanishi Kuniaki, Morishita Ryuichi, Kaneda Yasufumi, Uenoyama Maki, Ikeda Tomosumi, Fujikawa Kyosuke
Department of Orthopaedic Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Neurosci Res. 2005 Aug;52(4):299-310. doi: 10.1016/j.neures.2005.04.004.
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 electrophysiologically and histologically, and suggest that HGF gene transfer has potential for the treatment of crushed nerve.
众所周知，肝细胞生长因子（HGF）参与多种生物学功能，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，我们使用非病毒的日本血凝病毒（HVJ）脂质体方法，反复进行人HGF基因的肌肉注射，以研究该基因转染大鼠神经系统是否能够发挥神经营养作用，促进损伤神经的恢复。HGF蛋白和HGF mRNA的表达表明，基因确实通过逆行轴突运输进入了神经系统。在损伤后4周，对损伤神经进行电生理检查发现，反复注射HGF基因后，平均潜伏期显著缩短，平均最大M波振幅显著增大。此外，组织学结果显示，反复注射HGF基因的组中，轴突的平均直径、轴突数量和轴突总数均显著更大。上述结果表明，反复将人HGF基因转入大鼠神经系统能够在电生理和组织学方面促进损伤神经的恢复，并提示HGF基因转移在治疗损伤神经方面具有潜力。
