Contribution of cytochrome P450 products, EETs & 20HETE, on cerebral vasospasm

细胞色素P450产品、EET的贡献

• 批准号: 13671610
• 负责人: OKAMOTO Hirotsugu
• 金额: $ 2.62万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671610/
• 关键词: Cytochrome P450; EET; HETE; Aradiclonic acid; Cerebral vasospasm; Subarachnoid hemorrhage; Cerebral blood flow; Cerebral hemorrhage; 20HETE; 脳虚血

We developed the system in which we could measure changes of pial artery diameter, and changes in cerebral blood fow in rats. By using this system, we found that acute fall in cerebral blood flow and diameter after subarachnoid hemorrhage (SAH) was prevented by the inhibitor of 20-HETE, 17-ODYA. We also found that the concentration of 20HETE was increased after SAH, and this increased level of 20-HETE was attenuated by the inhibitor. Furthermore, if we simultaneously block 20-HETE production and increased EETs levels by the another inhibitor, we could successfully reverse the acute fall of cerebral blood flow.Therefore, from our study, it is suggested that the production of 20-HETE and may be the fall in EETs levels after SAH contributes to the acute fall in cerebral blood flow (acute cerebral vasospasm). Further, the inhibition of 20-HETE production and administration of EETS may give us therapeutic insights after SAH.

我们研制了一套能测量大鼠软脑膜动脉直径变化和脑血流变化的系统。通过使用该系统，我们发现20-HETE抑制剂17-ODYA可防止蛛网膜下腔出血（SAH）后脑血流量和脑直径的急性下降。我们还发现SAH后20-HETE的浓度增加，并且这种增加的20-HETE水平被抑制剂减弱。此外，如果我们用另一种抑制剂同时阻断20-HETE的产生和升高的雌二醇水平，我们可以成功地逆转脑血流量的急性下降。因此，从我们的研究中可以看出，SAH后20-HETE的产生和雌二醇水平的下降可能有助于脑血流量的急性下降（急性脑血管痉挛）。此外，抑制20-HETE的生产和管理EETS可能会给我们的治疗见解SAH后。

项目成果

岡本浩嗣: "COX NOS CYP450と脳循環・麻酔薬"Journal of Anesthesia. Suppl(印刷中). (2003)

Hirotsugu Okamoto：“COX NOS CYP450 和脑循环/麻醉”麻醉杂志增刊（2003 年）。

岡本浩嗣 他: "デクスメデトミジンの脳虚血再灌流後の反応性充血に対する影響"神経麻酔・集中治療. 6. 40-41 (2003)

Hirotsugu Okamoto 等：“右美托咪定对脑缺血再灌注后反应性充血的影响”《神经麻醉和重症监护》(Neuroanesthesia and Intense Care) 6. 40-41 (2003)。

H.Okamoto., et al.: "Cebral hyperemic responses after reperfusion under dexamedetomidine"Neuroanesthesia and Criticalcare. 6. 40-41 (2003)

H.Okamoto. 等人：“右美托咪定再灌注后的脑充血反应”神经麻醉和重症监护。

岡本浩嗣: "COX NOX CYP450と脳循環・麻酔薬"Journal of Anesthesia. Suppl(印刷中). (2003)

Hirotsugu Okamoto：“COX NOX CYP450 和脑循环/麻醉”麻醉杂志增刊（2003 年）。

H.okamoto., et al.: "Cerebral vasoresponses according to blood pressure changes in dexamedetomidine anesthesia"Neuroanesthesia and Critical care. 5. 31-32 (2002)

H.okamoto., et al.：“根据右美托咪定麻醉中血压变化的脑血管反应”神经麻醉和重症监护。