肝腫瘍に対する局所活性酸素誘導療法の、抗腫瘍効果の機序解明の研究

阐明局部活性氧诱导治疗肝肿瘤抗肿瘤作用机制的研究

• 批准号: 08770972
• 负责人: 山野井 彰
• 金额: $ 0.58万
• 依托单位: Shimane Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-08770972/
• 关键词: Oxygen free radical; Ischemia; Liver cancer; Nitric oxide

肝腫瘍に対する肝動脈反復遮断療法は、肝の阻血、再灌流によって局所誘導される活性酸素の細胞毒性理論に基づく癌治療法である。本年度は、4例の切除不能肝癌患者に本法を臨床応用した。肝細胞癌の1例で、側副血行路の完全郭清の後本法を行ったところ、腫瘍の著明な壊死、縮小を認めた。局所での活性酸素発生を効率的に誘導し、抗腫瘍効果を増強するためには、側副血行路の発達を可能な限り抑制する必要があると考えた。実験的研究では、血管拡張物質として重要な生理活性機能を持つと同時に抗腫瘍活性物質という二面性を有すNitric Oxide(以下NO)が、肝の阻血・再灌流障害に及ぼす影響を検討した。雑種成犬18頭を、強力な血管収縮作用を有し臓器虚血の原因となるEndothelin(以下ET)の拮抗剤(TAK-044)投与下に、NO放出剤(FK-409)の門脈内投与法の違いで以下の3群に分け、90分間の肝阻血を行った。NO大量群;TAK5mg/kg阻血前投与+FK3.2mg/kg再灌流時投与(n=6)NO少量群;TAK5mg/kg阻血前投与+FK0.4mg/kg再灌流時投与(n=6)コントロール群;生理食塩水投与(n=6)再灌流後の血中肝逸脱酵素の上昇は、NO大量群が最も高く、以下コントロール群、NO少量群の順にそれぞれ有為に抑制された。肝組織血流はNO大量群とNO少量群いずれもコントロール群より有為に良好であった。すなわち至適量のNOは、ET拮抗剤との協調で肝組織血流を維持し、阻血・再灌流障害を軽減するが、再灌流時の大量のNO放出は逆に障害を増強することが明らかとなった。NOは活性酸素と反応し、より強力な細胞毒性を持つPeroxy-nitrite(ONOO)を産生することから、局所誘導された活性酸素の抗腫瘍効果の一機序としてNOの関与が示唆された。

The theory of cytotoxicity of active acidins was guided by the anti-blocking method of liver movement, the method of blocking blood and reperfusion of liver, and the basic method of cancer treatment. This year, 4 patients with unresectable liver cancer were treated with this method. After the complete Guo Qing of liver cancer and accessory blood route in 1 case of liver cancer, this method was used to treat death, death and small death. According to the regulation of active acid production rate, the results of anti-drug therapy, anti-drug therapy, and accessory blood pathway may be limited, and the necessary measures may be tested. According to the results of the study, the important physiological activity mechanisms of vascular substances and antioxidants are Nitric Oxide (the following NO), liver blocking blood and reperfusion injury and so on. In 18-year-old adult dogs, forced vasodilator vasoconstriction was caused by hypovolemic blood loss. Endothelin (following ET) antagonist (TAK-044), NO (FK-409) were injected into three groups of dogs, and liver blood blockage was performed within 90 minutes. A large number of NO, a small amount of NO before TAK5mg/kg and + FK3.2mg/kg reperfusion, a small amount of TAK5mg/kg before and + FK0.4mg/kg reperfusion, a large number of liver dezymes in the blood after reperfusion, a high level of liver dezymes in the blood after reperfusion, a high peak of a large number of NO, a small number of the following groups, and a small amount of NO were significantly inhibited. The blood flow of liver tissue showed that a large amount of NO and a small number of NO groups showed good blood flow. The blood flow of the liver tissue was maintained by NO, ET antagonist, blood block and reperfusion injury, and a large amount of NO was released during reperfusion. it is necessary to strengthen the response of the liver tissue. NO active acidins reverse response, potency cytotoxicity test Peroxy-nitrite (ONOO) bioactive acid antiviral drugs, local lead bioactive acids antiviral drugs. The sequence of NO tests and signs of instigation were analyzed.