くも膜下出血における血管内皮細胞障害 : 血管内手術と開頭手術の比較 : 脳血管障害の最先端  [in Japanese] Endothelial Perturbation after Subarachnoid Hemorrhage: Impact of Open and Endovascular Surgery  [in Japanese]

血管内皮細胞は, 正常な状態においては, 血管を保護する機能を有しているが, 炎症反応が生じた場合には, 接着因子が産生され, 白血球の癒着や遊走が生じ, 向凝固状態となり, 血管透過性も亢進し, 内皮細胞機能が低下する. くも膜下出血後にも, このような血管内皮細胞における炎症反応が惹起されて, その後に生じる血管攣縮や, 凝固の亢進に影響を与えている可能性がある. また, 開頭クリッピング術と血管内手術による塞栓術を比較した場合, 開頭手術における手術侵襲が血管内皮細胞の炎症反応に与える影響は, 分子生物学的に明確にはなってはいない. そこで, われわれは, 基礎研究によってくも膜下出血後の血管内皮細胞障害について, 特にくも膜下出血にさらに脳への直接的ダメージが加わったと想定したモデルを作成し, 分子生物学的にアプローチした. さらに, 臨床研究として開頭手術患者と血管内手術患者における血中に存在する内皮細胞障害のマーカーを比較し, 手術手技によって内皮細胞障害に違いがあるのかどうかを検討した.

Endovascular coil emobolization has emerged as an alternative treatment of ruptured intracranial aneurysms, and it has reduced the therapeutic assault, on vessels. However, it is not clear what happens between such therapeutic assault and vascular response on a molecular level. We investigated endothelial cell disorder after subarachnoid hemorrhage (SAH) and the impact of open and endovascular surgery. In rat SAH models, we confirmed the endothelial perturbation such as the expression of interleukin 1-β, plasminogen actibator inhibitor-1 (PAI-1), von Willebrand factor (vWF), E-selectin, and apoptosis-related products that caused the morphological changes of endothelial cells. In a real-time RTPCR study, direct brain damage by a cold injury after experimental SAH emphasized the expression of p38 mitogen-activated protein kinase (p38 MAPK) in endothelial cells. In 36 SAH patients, the serum markers of endothelial cell disorder such as PAI-1, VWF and E-selectin that exist in the lower stream of p38 MAPK were compared between endovascular coil embolization (18 pat,ients) and open surgery (18 patients). The levels of serum markers of endothelial cell disorder in open surgery were statistically higher than endovascular surgery (p<0.05). These results indicate that the therapeutic assault on the endothelial cells in open surgery may be higher than that in endovascular coil embolization.