Pharmacological investigation of roles of cyclic flow reductions in the development of cerebral infarction

循环流量减少在脑梗死发展中作用的药理学研究

• 批准号: 12672211
• 负责人: UMEMURA Kazuo
• 金额: $ 1.66万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672211/
• 关键词: Ischemic reperfusion; Cerebral hemorrhage; Heparin; 脳梗塞; 動物実験; GPIIb; IIIa

Animal models in which cyclic flow reductions are reproducibly observed have been not reported. Therefore, we tried to establish a new model with cyclic flow reductions in cerebral circulation. We establish the model using photochemical thrombosis technique, which has been developed in our institute. Using this model, we investigated roles of cyclic flow reductions in the development of cerebral infarction. Antithrombotic agents and thrombolytic agents have fetal side effects of cerebral hemorrhage. However, mechanisms of cerebral hemorrhage is still unclear and the predict is impossible. Although cyclic flow reductions are thought to contribute to cerebral hemorrhage, the mechanisms is unclear. Therefore, we investigated by what mechanisms heparin, an antithrombotic agent causes cerebral hemorrhage. In the rabbit cerebral thrombosis model, heparin caused cerebral hemorrhage and then worsen neurological symptoms. A radical scavenger inhibited cerebral hemorrhage produced by heparin and reduced cerebral infarct size. Based on these findings, free radical may play a key role in cerebral hemorrhage. Although free radical may damage vessel wall and then cause cerebral hemorrhage, further investigate may be required.

尚未报道可重复观察到循环性血流减少的动物模型。因此，我们试图建立一个新的模型与循环流量减少的脑循环。本研究采用本所自行研制的光化学血栓形成技术建立大鼠脑缺血再灌注模型。利用该模型，我们研究了循环性血流减少在脑梗死发展中的作用。抗血栓药物和溶栓药物对胎儿脑出血有副作用。然而，脑出血的发病机制尚不清楚，无法预测。虽然循环性血流减少被认为是脑出血的原因，但其机制尚不清楚。因此，我们研究了抗血栓药物肝素引起脑出血的机制。在兔脑血栓模型中，肝素引起脑出血，继而加重神经系统症状。自由基清除剂抑制肝素引起的脑出血，并减少脑梗死面积。自由基可能在脑出血中起重要作用。虽然自由基可能损伤血管壁而导致脑出血，但仍需进一步研究。

项目成果

Takamatsu H.: "Change of local cerebral blood flow in photochemically-incluced thrombotic occlusion model in rats"Eur J Pharmacol. 398. 375-379 (2000)

Takamatsu H.：“大鼠光化学血栓闭塞模型中局部脑血流的变化”Eur J Pharmacol。

Zhao B.Q.: "A novel MCA occlusion model of thrombotic ischemia with cyclic flow reductions : development of cerebral hemorrhage induced by heparin"Brain Res Protocol. 9. 85-92 (2002)

赵北清：“一种新型的伴有循环流量减少的血栓性缺血的 MCA 闭塞模型：肝素诱导的脑出血的发展”Brain Res Protocol。

Suzuki Y: "A novel guinea pig model with cyclic flow reductions following thrombotic cerebral ischemia"Brain Res Protocol. 10. 55-59 (2002)

Suzuki Y：“血栓性脑缺血后循环流量减少的新型豚鼠模型”Brain Res Protocol。

Zhao B.Q.: "Cerebral hemorrhage due to heparin limits its neuroprotective effects : studies in a rabbit model of photothrombotic middle cerebral artery occlusion"Brain Res. 902. 30-39 (2001)

赵北清：“肝素引起的脑出血限制了其神经保护作用：光血栓性大脑中动脉闭塞兔模型的研究”Brain Res。

Kawano K: "Thromboxane A2 synthase inhibitor enhanced antithrombotic efficaccy of GPIIb/IIIa recceptor antagonist without increasing bleeding"Eur J Pharmacol. 417. 217-222 (2001)

Kawano K：“血栓素 A2 合酶抑制剂增强 GPIIb/IIIa 受体拮抗剂的抗血栓功效而不增加出血”Eur J Pharmacol。