Introduction of prostacyclin synthase gene for treatment of cerebral vasospasm

脑血管痉挛是蛛网膜下腔出血的严重并发症，常发生于脑动脉瘤破裂后，但其发病机制尚不清楚。脑血管痉挛是一种独特的临床现象，其特征在于主要脑动脉的延迟和延长收缩。蛛网膜下腔出血引起内皮功能障碍和内皮衍生的舒张因子的抑制。然后，恢复内皮源性舒张因子可以治疗这种现象。内皮源性舒张因子的代表是NO，在实验性SAH模型中导入NO合成酶基因治疗脑血管痉挛。我们关注了另一种内皮源性舒张因子前列环素（PGI 2），并采用等长张力记录法检测了PGI 2（贝前列素钠）的药理作用。贝前列素钠不能抑制高剂量钾（80 mM）引起的收缩。也不能抑制100 μmol/L去甲肾上腺素引起的收缩。贝前列素钠10、100 μmol/L、1 mmol/L可剂量依赖性地抑制10 μmol/LPGF 2 α引起的收缩。然而，贝前列素钠的收缩抑制作用可能不足以治疗SAH后的脑血管痉挛。因此，我们认为导入PGI_2合成酶基因对SAH后严重的脑血管收缩有很大的抑制作用是困难的。PGI_2有可能成为治疗脑血管痉挛的新药物，但仍需进一步研究。

Cerebral vasospasm is a severe complication of subarachnoid hemorrhage that frequently arises after rupture of a cerebral aneurysm, but the pathogenesis is still unclear. Cerebral vasospasm is a unique clinical phenomenon characterized by the delayed and prolonged contraction of the major cerebral arteries. subarachnoid hemorrhage causes dysfunction of endothelium, and inhibition of endothelium-derived relaxing factor. Then, restoration of endothelium derived relaxing factor may treat the phenomenon. The representative endothelium-derived relaxing factor is NO. Introduction of NO synthetase gene treat cerebral vasospasm in experimental SAH model. We paid attention to another endothelium-derived relaxing factor, prostacycline (PGI2), and tested pharmacological effect of PGI2 (beraprost sodium) using isometric tension recording. The beraprost sodium could not inhibit the contraction induced by high dose potassium (80mM). And, that could not inhibit the contraction induced by 100 μmol/L norepinephrine, too. The beraprost sodium 10, 100 μmol/L, 1 mmol/L could inhibit the contraction induced by 10 μmol/L PGF2α, dose-dependently. However, the contractile inhibition effect of beraprost sodium might not be sufficient for the treatment of cerebral vasospasm after SAH. Then, We thought it difficult that introduction of PGI2 synthetase gene had a great inihibitory effect to the severe cerebral vasoconstriction after SAH. PGI2 may have a possibility to be new therapeutic agent for cerebral vasospasm, however the further studies were required.