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脊髄損傷に対するHepatocyte Growth Factorの有効性の確立

确定肝细胞生长因子对脊髓损伤的有效性

基本信息

批准号：
18791057
负责人：
北村和也
金额：
$ 2.18万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

われわれは成体SDラットの胸髄損傷後急性期に、HGF受容体であるc-Metの発現は急速に上昇するのに比べてHGFの発現は緩除に上昇するために、損傷後急性期脊髄内でHGFが不足していることを発見したそこでherpes simplex virus l HSV-1) vectorを損傷3日前に直接脊髄に注入し、同部に圧挫損傷を作成しHGFの有効性を検討した。損留後急性期にはニューロンおよびオリゴデンドロサイトのアポトーシスを抑制し、血管新生を促進することで損傷範囲を縮小し、慢性期にかけてセロトニン線維の再生を促進することで良好な後肢運動機能回復が得られることを報告した。次に臨床応用を目指し、成体SDラットの第10胸髄圧挫損傷モデルに損傷直後よりrecombinant humanHGF (rhHGF)を2週間持続投与したところ、rhHGFの脊髄損傷部への高卒な導入がELISA法にて確認され、有意に良好な下肢運機能回復を認めた。またrhHGF群では残存する髄鞘面積が損傷中心部においても有恩に保たれており、損傷部空洞形成面積も著明に抑制されていることが明らかとなった。さらにはコモンマーモセット第5頸髄レベルに圧挫損傷を作製し直後より同様にrhHGFを4週間持続投与したところ、Bar ip testおよびopen field scoring共に有意に良好な運動機能回復を認めた。さらには損傷後12週目のMR像(T2WI)より、空洞形成ならびに常高信号領域がrhHGF群で著明に縮小していることが明らかとなった。これらの結果より、rhHGFを損傷にくも膜下腔に持続投与する治療法が、霊長類脊髄霜傷に対しても有効であることが明らかとなった。今回の結果は、本治療法のヒト脊髄損傷に対する有効性を大きく示唆するものと考える。

In the acute stage after injury, the expression of HGF receptor c-Met increased rapidly, and the expression of HGF decreased slowly. In the acute stage after injury, the expression of HGF decreased rapidly. In the acute stage after injury, the expression of HGF decreased rapidly. In the acute stage after injury, the injury, the expression of HGF decreased rapidly. In the acute stage after injury, the injury, the expression of HGF decreased rapidly. In the acute stage after injury After the injury, the acute phase of the injury was reduced, and the chronic phase of the injury was improved. The recovery of hind limb motor function was reported. The 10th thoracic injury in adult SD rats was confirmed by ELISA after continuous administration of recombinant human HGF (rhHGF) for 2 weeks. The area of the sheath where the HGF remains is the area where the damage center is protected, and the area where the damage cavity is formed is the area where the damage is inhibited. The 5th neck of the patient was injured by stress, and the 5th neck was injured by stress. The 5th neck was injured by stress, and the 5th neck was injured by stress. The 5th neck was injured by stress, and the 5th neck was injured by stress. The 5th neck was injured by stress, and the 5th neck was injured by stress. The 5th neck was injured by stress. The 5th neck was injured by stress, and the 5th neck was injured by stress. The 5th neck was injured by stress, and the 5th neck was injured by stress. The 5th neck was injured by stress, and the 5th neck was injured by stress. The 5th neck was injured by stress. The 5th neck was injured by stress, and the 5th neck was injured by stress. The 5th neck was injured by stress. The 5th neck was injured by stress, and the 5th neck was injured by stress. The 5th neck was injured by stress, and the 5th neck was injured by stress. The 5th MR imaging (T2WI) was observed 12 weeks after injury. Voids were formed and high signal intensity areas were observed. The result is that the rhHGF can be injected into the lower part of the membrane. The results of this study indicate that the treatment of spinal cord injury is effective.