Development of inhibitor-resistant lung surfactant

抗抑制剂肺表面活性物质的开发

• 批准号: 10470316
• 负责人: KOBAYASHI Tsutomu
• 金额: $ 6.53万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470316/
• 关键词: ARDS; surfactant; dextran; surfactant protein; surfactant inhibitor; surface activity; palmitoyl radical; polymer; 胎便吸入症候群; 血清蛋白質; 酸素化能; 呼吸機能; 肺サーファクタント; 急性呼吸急迫症候群; テキストラン; ポリエチレン・グリコール; 血液ガス; 肺コンプライアンス; 急性呼吸窮迫症候群; アルプミン; 表面吸着速度; 表面張力

In ARDS, surfactant inhibitors appear and cause respiratory failure. In studies to develop an inhibitor-resistant surfactant, the following results were obtained.(I) Effects of polysaccharides (dextran). (1) Addition of dextran (40-70kDa) to a mixture of surfactant and serum (a surfactant inhibitor) reversed the inhibited activity and increased tidal volumes of immature newborn rabbits. (2) In rats with ARDS, inhalation of aerosolized surfactant followed by aerosolized dextran improved the lung functions significantly better than that of aerosolized surfactant alone. (3) Dextran reduced surfactant inhibition by meconium, suggesting the therapeutic effects on meconium aspiration syndrome.(II) Modulation of surfactant proteins. (1) ARDS rats were treated with reconstituted surfactants consisted of synthetic phospholipids plus various doses of surfactant proteins B and C (SP-B ＆ SP-C). It was demonstrated that >0.7% in SP-B and >1.4% in SP-C were needed for the reconstituted surfactant to bring about the therapeutic effects. (2) Monomeric form of SP-C (mSP-C) which lacks palmitoyl radical in the molecular structure does not improve the physiologic function, but polymeric form of mSP-C shows the physiologic function better than normal SP-C.An application of polymeric form of mSP-C was strongly suggested for development of artificial surfactant to treat ARDS patients.(III) Additional studies. (1) In immature rabbits, positive end-expiratory pressure reversed serum-inhibited function of lung surfactant. (2) Surfactant replacement reversed respiratory failure caused by inhalation of fabric protector. (3) Propofol reduced inflamatory responses.

在ARDS中，抑制剂出现并引起呼吸衰竭。 ARDS，通过渗透性的葡萄糖蛋白的渗透性葡萄糖蛋白b和c（Sp-b＆sp-c）吸入了渗透性的表面活性剂。带来效果（2）单体形式的SP-C（MSP-C），该形式在分子结构中缺乏棕榈酰基，但MSP-C E生理功能比正常SP-C.AN的应用更好of Polymeric Form of MSP-C Was Strongly Sugested for Development of Artificial Surfactant to Trust Ards Patient. (2) Surfactant Replacement Respiratory Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure Failure故障故障故障故障故障故障故障故障故障故障故障失败吸入织物保护器。

项目成果

徐咏梅: "血清と終末呼気陽圧による加工天然サーファクタントの機能変化"日本界面医学会誌. 31・1. 57-65 (2000)

徐永梅：“血清和呼气末正压引起的加工天然表面活性剂的功能变化”日本表面医学会杂志31・1（2000）。

Tashiro,Katsumi: "Dextran reduces surfactant inhibition by meconium"Acta Paediatrica. 89. 1439-1445 (2000)

Tashiro，Katsumi：“右旋糖酐减少胎便对表面活性剂的抑制”Acta Paediatrica。

紺崎友晴: "血清によって阻害されたサーファクタントの活性に対するデキストランの効果:気泡拍動法と肺洗浄ラットによる評価"日本界面医学会誌. 31・1. 49-56 (2000)

Tomoharu Konsaki：“右旋糖酐对血清抑制的表面活性剂活性的影响：使用气泡脉动法和肺灌洗大鼠的评估”日本表面医学会杂志31・1（2000）。

Tashiro, K., et al.: "Modified natural and synthetically reconstituted surfactant therapies for acute lung injury"Acta Anaesthesiologica Scandinavica. 43・8. 821-828 (1999)

Tashiro, K. 等人：“用于急性肺损伤的改良天然和合成重组表面活性剂疗法”Acta Anaesthesiologica Scandinavica 43・8 (1999)。

鈴木康弘 ほか: "再構築表面活性物質における脂質およびアポ蛋白の組成と分布が表面活性に及ぼす影響"日本界面医学会雑誌. 30・1. 45-50 (1999)

Yasuhiro Suzuki 等：“脂质和脱辅基蛋白的组成和分布对重构表面活性剂材料表面活性的影响”日本表面医学会杂志 30・1（1999）。