EFFECTS OF VASOACTIVE AGENTS ON THE REGIONAL BLOOD FLOW AND THE PERMEABILITY IN MALIGNANT BRAIN TUMORS

血管活性药物对恶性脑肿瘤局部血流和通透性的影响

• 批准号: 03454349
• 负责人: FUKUI Masashi
• 金额: $ 4.22万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454349/
• 关键词: malignant glioma; vasoactive agents; regional blood flow; tumor vessels; 脳腫瘍; 化学療法; 血管作動性物質; 脳血流; 血液脳関門; 局所脳血流

The research project was aimed to study effects of vasoactive agents on the regional cerebral blood flow (rCBF) and the permeability in malignant brain tumors. We studied the effect of the intracarotid administration of various vasoactive agents on the rCBF in brain tumors by hydrogen clearance method using a rat glioma model. The brain tumor vessels are structually and biochemically different from the normal brain vessels, and show an altered response to vasoactive agents, such as histamine, adenosine, ATP, prostacycline (PGI_2), and calcium antagonists. In our experiment, these agents have elevated the rCBF in the brain tumor significantly without affecting the systemic vital signs and the rCBF in the ipsilateral normal brain tissue. The tumor selective percent increase of the rCBF ranged from 30 to 100 % with these agents. Although the mechanism of altered response of the rCBF in the brain tumor vessels should be further investigated, these vasoactive agents are considered to have the potential to be utilized to selectively increase drug deliverry to malignant glioma in the brain.

本研究旨在探讨血管活性药物对恶性脑肿瘤局部脑血流量（rCBF）和通透性的影响。采用氢清除法研究了不同血管活性药物对大鼠脑胶质瘤rCBF的影响。脑肿瘤血管在结构和生化上与正常脑血管不同，并且对血管活性剂如组胺、腺苷、ATP、前列环素（PGI_2）和钙拮抗剂的反应发生改变。在我们的实验中，这些药物在脑肿瘤中显著升高rCBF，而不影响全身生命体征和同侧正常脑组织中的rCBF。这些药物的肿瘤选择性rCBF增加百分比范围为30%至100%。虽然脑肿瘤血管中rCBF反应改变的机制还有待进一步研究，但这些血管活性药物被认为具有选择性增加脑恶性胶质瘤药物递送的潜力。

项目成果

Nomura T,Ikezaki K,Matsukado K,Fukui M: "Effects of prostacyclin analogue ilopost on the regional cerebral blood flow in transplanted rat brain tumor." Neurol Res. 15. 401-404 (1993)

Nomura T、Ikezaki K、Matsukado K、Fukui M：“前列环素类似物 ilopost 对移植性大鼠脑肿瘤局部脑血流的影响。”

Ikezaki K, Nomura T, Takahashi M, et al: "MRI Contrast Enhancement by Mn-TPPS in Experimental Rat Brain Tumor with Peripheral Benzodiaxpine Receptors" J Neuronsurg. in press.

Ikezaki K、Nomura T、Takahashi M 等人：“Mn-TPPS 在具有外周苯并二嗪受体的实验性大鼠脑肿瘤中通过 Mn-TPPS 增强 MRI 对比度”J Neuronsurg。

Nomura T, Ikezaki K, Natori Y, Fukui M: "Altered response to histamine in brain tumor vessels : The selective increase of regional cerebral bolld flow in transplanted rat brain tumor" J Neuronsurg. 79. 722-728 (1993)

Nomura T、Ikezaki K、Natori Y、Fukui M：“脑肿瘤血管中组胺反应的改变：移植性大鼠脑肿瘤中局部脑血流的选择性增加”J Neuronsurg。

Nomura T, Ikezaki K, Matsukado K, Fukui M: "Effects of prostacyclin analogue ilopost on the regional cerebral blood flow in transplanted rat brain tumor" Neurol Res. 15. 401-404 (1993)

Nomura T、Ikezaki K、Matsukado K、Fukui M：“前列环素类似物 ilopost 对移植性大鼠脑肿瘤局部脑血流的影响”Neurol Res。

Nomura T,Ikezaki K,Matsukado K,Fukui M: "Effects of prostacylin analogueilopost on the regional cerebral bloodflow in transplanted rat brain tumor." Neurol Res. 15. 401-404 (1993)

Nomura T，Ikezaki K，Matsukado K，Fukui M：“前列环素类似物对移植性大鼠脑肿瘤局部脑血流的影响。”