体外循環による腎機能障害に対する亜硝酸塩の腎保護効果の検討と分子機序の解明

亚硝酸盐对体外循环所致肾功能障碍的肾保护作用考察及分子机制的阐明

• 批准号: 22K09074
• 负责人: 大野 翔
• 金额: $ 2.25万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K09074/
• 关键词: 亜硝酸塩; 腎保護効果; 急性腎障害; 体外循環

体外循環後の急性腎障害に対する亜硝酸塩の腎保護効果を検討するためにラット人工心肺ー急性腎障害モデルを作成した．腎障害は腎組織の腎障害マーカー（KIM-1）のmRNAの発現量が上昇することを確認した．また亜硝酸塩の至適投与量を検討するため，亜硝酸塩を0.3 mg/kg，1.0 mg/kg，2.0 mg/kg，3.0 mg/kg静注し，体外循環開始5分時点での血中濃度を測定した．2.0 mg/kgの投与で臓器保護効果を発揮する10~20 nMに収まっていることを確認した．ラット人工心肺ー急性腎障害モデルにおいて，体外循環前の亜硝酸塩2 mg/kg静注が腎保護に関わるかを検討するためにSham群（カニュレーションのみ），人工心肺群，人工心肺＋亜硝酸塩群の3群の比較検討を行った．各群5例ずつ行った予備実験では亜硝酸塩の腎保護効果が期待できる結果となった．腎保護効果の分子機序に迫るためにミトコンドリア機能やミトコンドリアの癒合．分裂に関わるタンパク質のmRNA，活性酸素に関わるタンパク質のmRNA，腎レニンのmRNA，溶血への関与等を検索したが，仮説を証明するに足りる結果とならなかった．現在同様のプロトコルで盲検化し，本実験を遂行中である．作用機序に関しては上記と同様の検討は行うが，網羅的解析（RNA-sequence）等も検討する．

After the in vitro circulation of the environmental protection agent, the chemical nitrate was used to protect the artificial heart and lungs. the tissue of the artificial heart and lung was tested. The tissue of the artificial heart and lung was damaged. The tissue of the artificial heart and lung was damaged. The tissue of the artificial heart and lung was damaged. The tissue of the artificial heart and lung was damaged. The tissue of the artificial heart and lung (KIM-1) was tested on the mRNA valve to make sure that it was confirmed. The nitric acid was used to make sure that it was confirmed. The nitric acid was used to inject and measure the amount of nitrate, and the nitric acid was 0.3 mg/kg. 1. 0 mg/kg,2.0 mg/kg,3.0 mg/kg intravenous infusion, 5 minutes after in vitro start-up, blood titration assay. 2. 0 mg/kg infusion and device protection. Results: 10. 20 nM emergency response was confirmed. Artificial cardiopulmonary bypass for acute heart and lung injury. The artificial heart and lung group (Sham group) was injected intravenously by intravenous injection of prostaglandin nitrate 2 mg/kg in vitro. The artificial heart and lung plus nitric acid group 3 were better than the control group. 5 cases in each group were tested, and the results of nitric acid protection were expected. The molecular order of the molecular mechanism of the protection of the heart and lung was compelled to make sure that the machine was successfully linked. The cleavage products were isolated from the mRNA, and the active acid was isolated from the mRNA. The mRNA, hemolysis and isoprenaline profiles were detected, and the results were verified. Now that the same protocol is blinded, this device is in operation. The function of the system is to determine the number of users in the network, such as the RNA-sequence, and so on.