Prevention and treatment of chronic lung disease of the newborn infants

新生儿慢性肺病的防治

• 批准号: 11470223
• 负责人: ARAKAWA Hiroshi
• 金额: $ 7.3万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470223/
• 关键词: Chronic lung disease; Pulmonary surfactant; Surfactant subtype; High frequency oscillatory ventilation; Congenital alveolar proteinosis; Surfactant protein B; Cytokine; Autoantibody; 炎症性サイトカイン; 気道吸引液; サーファクタント蛋白質B; 高頻度振動換気法; 活性型肺サーファクタント; 超低出

The incidence of chronic lung disease (CLD) reaches 20% of the very low birth weight infants. In the present study, we tried to understand the pathogenesis of CLD and develop strategy for prevention and treatment of CLD.1)Subfractions of pulmonary surfactant under high frequency oscillatory ventilationWe made a rabbit model of acute respiratory distress syndrome, then performed conventional mandatory ventilation (CMV) or high frequency oscillatory ventilation (HFOV). After 4h ventilation, bronchoalveolar lavage fluid was collected. Surfactant subtype was fractionated using ultracentrifugation and surfactant subtype conversion was evaluated in each ventilatory mode. We could demonstrate that HFOV was superior to CMV in terms of surfactant subtype conversion.2)Congenital alveolar proteinosis and surfactant protein B deficiency in JapanCongenital alveolar proteinosis (CAP) is classified into type VI CLD. Two cases of CAP and one case of partial surfactant protein B(SP-B) deficiency were identified in Japan between 1998 and 2002. Typical SP-B deficiency with a frame shift mutation, 121ins2, leading to a truncated nonfunctional SP-B, was not identified. We also analyzed abundance of the deletion form of SP-B mRNA, i.e., alternatively spliced SP-B mRNA in 3 cases of CAP. The contents of the "minor" SP-B mRNA in those patients were higher as compared to those in normal lungs.3)Anti-IL-8 autoantibody in the tracheobronchial aspirates in infants with CLDWe reported previously a large amount of IL-8 in tracheobronchial aspirates during the early stage of life in type III CLD. In the present study, anti-IL-8 IgM antibody in infants with type III CLD was significantly higher as compared to type I, type II, and type V CLD. The presence of anti-IL-8 autoantibody seems to be the mechanism that limits the bioavailability of free IL-8 in the lung.

在极低出生体重儿中，慢性肺病（CLD）的发病率达到20%。本研究旨在探讨慢性肺疾病的发病机制，并为慢性肺疾病的防治提供理论依据。1）高频振荡通气对肺表面活性物质亚组分的影响建立家兔急性呼吸窘迫综合征模型，分别进行常规指令通气（CMV）和高频振荡通气（HFOV）。通气4 h后收集支气管肺泡灌洗液。使用超离心分离表面活性剂亚型，并在每种分离模式下评价表面活性剂亚型转换。我们可以证明HFOV在表面活性物质亚型转换方面上级CMV。2）日本先天性肺泡蛋白沉积症和表面活性物质蛋白B缺乏症先天性肺泡蛋白沉积症（CAP）被分类为VI型CLD。1998年至2002年间，日本发现了2例CAP和1例部分表面活性蛋白B（SP-B）缺乏症。未发现典型的SP-B缺陷伴移码突变121 ins 2，导致SP-B截短无功能。我们还分析了SP-B mRNA缺失形式的丰度，即，3例CAP中存在选择性剪接的SP-B mRNA。3）CLD患儿气管支气管吸出物中的抗IL-8自身抗体我们曾报道III型CLD患儿早期气管支气管吸出物中存在大量IL-8。在本研究中，与I型、II型和V型CLD相比，III型CLD婴儿的抗IL-8 IgM抗体显著较高。抗IL-8自身抗体的存在似乎是限制游离IL-8在肺中的生物利用度的机制。

项目成果

清水 浩, 荒川 浩, 小俣 真, 佐野仁美, 小川雄之亮: "肺胞蛋白症"日本胸部臨床. 59. 256-262 (2000)

Hiroshi Shimizu、Hiroshi Arakawa、Makoto Omata、Hitomi Sano、Yunosuke Okawa：“肺泡蛋白沉着症”日本胸科诊所。

清水 浩, 荒川 浩, 小俣 真, 菅原志保子, 小川雄之亮: "肺サーファクタント蛋白質Bの遺伝子変異と呼吸器疾患"THE LUNG perspectives. 9・4. 471-476 (2001)

Hiroshi Shimizu、Hiroshi Arakawa、Makoto Omata、Shihoko Sukawara、Yunosuke Okawa：“肺表面活性蛋白 B 的基因突变与呼吸系统疾病”THE LUNG 471-476 (2001)。

Kakinuma R., Shimizu H., Ogawa Y.: "Effect of meconium on the rate of in vitro subtype conversion of swine pulmonary surfactant."European Journal Pediatrics. 161. 31-36 (2002)

Kakinuma R.、Shimizu H.、Okawa Y.：“胎便对猪肺表面活性物质体外亚型转化率的影响。”欧洲儿科杂志。

Hitomi Sano, Yoshio Kuroki, Hiroshi_Shimizu, Yunosuke Ogawa: "The surfactant components modulate the immune response to lipopolysaccharides (in Japanese)"J Jpn Med Soc Biol Interface. 32. 86 (2001)

Hitomi Sano、Yoshio Kuroki、Hiroshi_Shimizu、Yunosuke Okawa：“表面活性剂成分调节对脂多糖的免疫反应（日语）”J Jpn Med Soc Biol Interface。

高崎二郎, 小川雄之亮: "乳児慢性呼吸器疾患"小児科臨床. 55・4. 713-716 (2002)

高崎次郎、小川佑之助：“婴儿慢性呼吸道疾病”儿科 55・4（2002 年）。