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Brain and Nerve No to Shinkei Volume 43, Issue 7 （July 1991）

Brain and Nerve 脳と神経 43巻7号（1991年7月発行）

Japanese English

原著

Angiotensin II静注昇圧法によるラットグリオーマの脳腫瘍局所血流量および腫瘍内薬剤濃度に対する選択的増強効果についての検討 Selective Enhancement of Tumor Blood Flow and Drug Delivery to Brain Tumors in Experimental Rat Gliomas under Angiotensin II-Induced Hypertension 小笠原英敬 ¹ , 木矢克造 ¹ , 栗栖薫 ¹ , 堀田卓宏 ¹ , 三上貴司 ¹ , 杉山一彦 ¹ , 魚住徹 ¹ Hidenori Ogasawara ¹ , Katsuzo Kiya ¹ , Kaoru Kurisu ¹ , Takuhiro Hotta ¹ , Takashi Mikami ¹ , Kazuhiko Sugiyama ¹ , Tohru Uozumi ¹ ¹広島大学医学部脳神経外科 ¹Department of Neurosurgery, Hiroshima University School of Medicine キーワード： angiotensin II , experimental glioma , regional cerebral blood flow , etoposide , intracarotid infusion Keyword: angiotensin II , experimental glioma , regional cerebral blood flow , etoposide , intracarotid infusion pp.657-662

発行日 1991年7月1日 Published Date 1991/7/1

DOI https://doi.org/10.11477/mf.1406900222

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Abstract 文献概要
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　9L gliosarcoma cellを移植したラット脳腫瘍モデルを用いて，angiotensin II（AT II）静注による昇圧前後での，脳腫瘍と正常脳組織の局所血流量を，電解式およびレーザー式組織血流計により測定した。また，内頸動脈内投与したetoposideの腫瘍内および正常脳組織内濃度を昇圧群と非昇圧群とで比較検討した。1）昇圧負荷前の局所血流量は，正常ラットのcaudate-putamenでは43.9ml／100g／minであったのに対し，担脳腫瘍ラットでは腫瘍内が28.2ml／100g／min，対側のcaudate-putamenが23.0ml／100g／minと正常ラットに比べいずれも低下していた。2）担脳腫瘍ラットの昇圧後の局所血流量は，腫瘍部では平均で昇圧前値の176％に増加したが，対側caudate-putamenでは昇圧前値の94％とわずかに減少した。3）etoposideの平均腫瘍内濃度は，併用昇圧動注群は単独動注群の約2.2倍に増加したが，正常脳組織内への移行は低かった。AT II静注による昇圧下では脳腫瘍の局所血流量と薬剤到達性が選択的に増加することが明らかとなり，本法は化学療法の抗腫瘍効果を増強する一助となることが示唆された。

Regional blood flow of brain tumors and normal brain tissue of rats before and during angiotensin II (AT II) -induced hypertension were measured using an electrolytic flowmeter and a laser flowmeter. Etoposide concentration in the tumor and brain tissue after intracarotid administration were also measured in brain tumor bearing rats with or with-out AT II-induced hypertension. A suspension of 5×105/10 μl 9L gliosarcoma cells was innoculated into the left caudate-putamen of CD Fischer 344 rats. Before induced hypertension, regional blood flow of the tumor (28.2±2.6ml/100 g/min ; mean±SEM) and the contralateral caudate-putamen (23.0±1.8ml/100g/min)) in the tumor bearing rats were significantly lower than that of the caudate-putamen (43.9±4.1ml/100g/min) in the normal rats (p＜0.01).

Intravenous administration of AT II at a dose of 0. 4-0.6μg/body/min increased the mean arterial blood pressure from 96.5±4.7mmHg to 138.0±3.6mmHg. AT II-induced hypertension resulted in an approximate 1.8 (1.1-3.6)- fold increase in the regional tumor blood flow. On the other hand the regional blood flow of the contralateral caudate-putamen was slightly decreased at the rate of 6%. The mean concentration of etoposide with AT II-induced hypertension in the tumor tissue was 2.2-fold higher than that without AT II-induced hyper-tension. However, etoposide delivery to normal brain tissue was small. From these results, induced hypertension with intravenously administrated AT II selectively increase the tumor blood flow and drug delivery to brain tumor tissue. Intracarotid chemo-therapy with AT II-induced hypertension might contribute to enhance therapeutic effect of malig-nant brain tumors.