Development of the new treatment of ischemic brain injury by regulating prostaglandin D2 synthesis

调控前列腺素D2合成治疗缺血性脑损伤新药的开发

• 批准号: 22591594
• 负责人: MASE Mitsuhito
• 金额: $ 3万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591594/
• 关键词: 脳梗塞; プロスタグランジン D2 合成酵素阻害剤; 霊長類モデル; 高次脳機能; prostaglandin D synthase; H-PGDS inhibitor; cerebral ischemia; monckey model; reperfusion; 虚血性脳損傷; プロスタグランジンD合成酵素; 再灌流障害

The purpose of this study is to clarify the efficacy of prostaglandin D2 synthase (PGDS) inhibitor on cerebral ischemia. We developed cerebral ischemia and reperfusion injury model using Cynomolgus monkeys. Ischemia was produced by a placement of a micro-catheter in the M1 portion of middle cerebral artery (MCA) for 3 hours, and reperfusion was made by withdrawal of the catheter. In this model, constant cerebral infarction in the MCA area was found. Usually, the animal died by cerebral herniation when infarct volume was more than 5000 mm3. In the treatment group, PGDS inhibitor (HQL79) was administer by oral one day before the ischemic insult. For one month monitoring, there was no side effect of this drug on the systemic condition and blood examinations of the animals. Brain edema after reperfusion (day 3) was tended to be reduced in the treatment group. One animal with 6689m3 of infarction volume survived. These results suggest that (PGDS) inhibitor may have a possibility to reduce ischemic brain injury. Further study will be needed to confirm this possibility.

本研究的目的是阐明前列腺素D2合成酶（PGDS）抑制剂对脑缺血的疗效。本研究采用食蟹猴建立了脑缺血再灌注损伤模型。通过在大脑中动脉（MCA）的M1部分放置微导管3小时产生缺血，并通过撤回导管进行再灌注。在该模型中，发现MCA区域存在持续性脑梗死，通常，当梗死体积超过5000 mm3时，动物死于脑疝。治疗组于缺血前1天口服PGDS抑制剂（HQL 79）。一个月的监测，该药物对动物的全身状况和血液检查没有副作用。治疗组再灌注后（第3天）脑水肿有减轻的趋势。1只动物存活，梗死体积为6689m3。提示PGDS抑制剂可能具有减轻缺血性脑损伤的作用。需要进一步研究来证实这种可能性。