Development of artificial lung surfactant

人工肺表面活性剂的研制

• 批准号: 05671254
• 负责人: KOBAYASHI Tsutomu
• 金额: $ 1.28万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671254/
• 关键词: lung surfactant; phosphatidylcholine; surfactant protein; immature rabbit; static lung volume; tidal volume; inhalation therapy; adult respiratory disterss syndrome; 動脈血酸素分圧; 超音波ネブライザー; 脂質; アポ・タンパク質; 呼吸窮迫症候群; 肺コンプライアンス

1. Development of artificial surfactantA) Investigation for the best composition of lipids (1993) : Activity of several reconstituted surfactants that consisted of synthetic dipalmitoylphosphatidylcholine (DPPC) , phosphatidylglycerol (PG) and dioleoylphosphatidylcholine (DOPC) with different ratios plus surfactant-associated proteins-B and-C (SP-B and SP-C) was evaluated in immature rabbits. The surfactant composed of DPPC : PG : DOPC at a ratio of 60 : 20 : 20 showed the best activity.B) Investigation for the best composition of proteins (1994) : Activity of several reconstituted surfactants that consisted of isolated lipids from lung plus different doses of SP-B and SP-C were evaluated in immature rabbits. The surfactant containing SP-B at 0.7% and SP-C at 1.4% improved the static pressure-volume relationship of the lung at the best, but the tidal volume was not completely normalized. Further studies are necessary for method to combine lipids and proteins.2. Treatment of adult repiratory distress syndrome (ARDS) with surfactantA) Intratracheal instillation method (1993) . Instillation of surfactant suspension (50 mg/ml, 2 ml/kg) into the trachea of rats with ARDS that induced by endotoxin (50 mg/kg) improved the arterial oxygen pressure (PaO_2) from 85 mmHg to 345 mmHg (P<0.05) , but caused hypotension.B) Administration of surfactant by inhalation (1994) : Inhalation of surfactant aerosol improved the PaO_2 of ARDS rats from 84 mmHg to 243 mmHg (P<0.05) without causing hypotension.Comments and conclusionsThe present results suggest that inhalation of aerosolized surfactant can apply for treatment of clinical ARDS.We should make haste to develope an effective artificial surfactant.

1. 脂质最佳组成的研究（1993）：用不同比例的合成双棕榈酰基磷脂酰胆碱（DPPC）、磷脂酰甘油（PG）和二油酰基磷脂酰胆碱（DOPC）与表面活性剂相关蛋白- b和c （SP-B和SP-C）组成的几种重组表面活性剂在幼兔体内的活性进行了评价。DPPC: PG: DOPC以60:20:20的比例组成的表面活性剂活性最好。B)最佳蛋白质组成的研究（1994）：几种重组表面活性剂的活性在未成熟家兔中进行了评估，这些表面活性剂由分离的肺脂质和不同剂量的SP-B和SP-C组成。含有0.7% SP-B和1.4% SP-C的表面活性剂对肺静压-容积关系的改善效果最好，但对潮气量没有完全归一化。脂质与蛋白质结合的方法有待进一步研究。表面坦坦气管内滴注法治疗成人呼吸窘迫综合征（ARDS）（1993）。内毒素（50 mg/kg）致急性呼吸窘迫综合征大鼠气管内注入表面活性剂悬浮液（50 mg/ml、2 ml/kg）可使动脉氧压（PaO_2）由85 mmHg提高至345 mmHg (P<0.05)，但引起低血压。B)吸入表面活性剂（1994）：吸入表面活性剂气雾剂可使ARDS大鼠PaO_2由84 mmHg提高到243 mmHg (P<0.05)，且未引起低血压。结论雾化表面活性剂吸入可用于临床ARDS的治疗。我们应该抓紧研制一种有效的人工表面活性剂。

项目成果

Nitta, Keiko et al.: "Impairment of surfactant activity and ventilation by proteins in lung edema fluid" Respir.Physiol.95. 43-51 (1994)

Nitta、Keiko 等人：“肺水肿液中蛋白质对表面活性剂活性和通气的损害”Respir.Physiol.95。

Tashiro, Katsumi et al.: "Aerosolized and instilled surfactant therapies for acute lung injury by intratracheal endotoxin in rats" Crit.Care Med.(in press).

Tashiro、Katsumi 等人：“雾化和滴注表面活性剂疗法治疗大鼠气管内内毒素引起的急性肺损伤”Crit.Care Med.（出版中）。

Tashiro,Katsumi: "Aerosolized and instilled surfactant therapies for acute lung injury by intratracheal endotoxin in rats" Critical Care Medicine. (in press).

Tashiro，Katsumi：“雾化和滴注表面活性剂疗法治疗大鼠气管内内毒素引起的急性肺损伤”重症监护医学。

Li,Wen-Zi: "Aerosolized surfactant reverses respiratory failure in lung-lavaged rats" Acta Anaesthesiologica Scandinavica. 38. 82-88 (1994)

李文子：“雾化表面活性剂逆转肺灌洗大鼠的呼吸衰竭”Acta Anaesthesiologica Scandinavica。

Li,Wen-Zhi: "Aerosolized surfactant reverses respiratory failure in lung lavaged rats" Acta Anaesthesiologica Acandinavica. 38. 82-88 (1994)

李文志：“雾化表面活性剂逆转肺灌洗大鼠的呼吸衰竭”Acta Anaesthesiologica Acandinavica。