Miyazawa T, Matsumoto K, Ohmichi H, Katoh H, Yamashima T, Nakamura T
Department of Neurosurgery, National Defense Medical College, Saitama, Japan.
J Cereb Blood Flow Metab. 1998 Apr;18(4):345-8. doi: 10.1097/00004647-199804000-00001.
Hepatocyte growth factor (HGF), a natural ligand for the c-met protooncogene product, exhibits mitogenic, motogenic, and morphogenic activities for regeneration of the liver, kidney, and lung. Recently, HGF was clearly shown to enhance neurite outgrowth in vitro. To determine whether HGF has a neuroprotective action against the death of neurons in vivo, we studied the effect of HGF on delayed neuronal death in the hippocampus after 5-minute transient forebrain ischemia in Mongolian gerbils. Continuous postischemic intrastriatal administration of human recombinant HGF (10 or 30 micrograms) for 7 days potently prevented the delayed death of hippocampal neurons under both anesthetized and awake conditions. Even when HGF infusion started 6 hours after ischemia (i.e., in a delayed manner), HGF exhibited a neuroprotective action. We conclude that HGF, a novel neurotrophic factor, has a profound neuroprotective effect against postischemic delayed neuronal death in the hippocampus, which may have implications for the development of new therapeutic strategies for ischemic neuronal damage in humans.
肝细胞生长因子（HGF）是原癌基因c-met产物的天然配体，对肝脏、肾脏和肺的再生具有促有丝分裂、促运动和促形态发生活性。最近，有明确证据表明HGF在体外可促进神经突生长。为了确定HGF在体内是否对神经元死亡具有神经保护作用，我们研究了HGF对蒙古沙鼠5分钟短暂性前脑缺血后海马体延迟性神经元死亡的影响。在缺血后连续7天纹状体内注射人重组HGF（10或30微克），在麻醉和清醒条件下均能有效预防海马体神经元的延迟性死亡。即使在缺血6小时后开始输注HGF（即延迟给药），HGF仍表现出神经保护作用。我们得出结论，HGF作为一种新型神经营养因子，对海马体缺血后延迟性神经元死亡具有显著的神经保护作用，这可能对人类缺血性神经元损伤新治疗策略的开发具有重要意义。
