Basic research on novel therapeutic approaches to lung injury associated with Legionella pneumophilia pneumonia.

嗜肺军团菌肺炎相关肺损伤新治疗方法的基础研究。

• 批准号: 16591813
• 负责人: KURAHASHI Kiyoyasu
• 金额: $ 2.37万
• 依托单位: Yokohama City University Graduate School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591813/
• 关键词: acute lung injury; ventilator induced lung injury; keratinocyte growth factor; lung protective strategy; gene therapy; reproduction; cytokines; hyperadc lung injury; レジオネラ肺炎; 高濃度酸素; 肺感染症; 肺損傷; レジオネラ; 肺炎; 肺傷害; 人工呼吸; アポトーシス; ventilator indu

We studied anesthetized and mechanically ventilated rats, in which the hepatic inflow was transiently interrupted twice for 15 minutes. Two tidal volumes, 6 ml/kg (IR-LT) and 24 ml/kg (IR-HT), were assessed after liver ischemia-reperfusion, as well as after a sham operation (NC-LT and NC-HT, respectively). Of the 4 groups, only the IR-HT group developed lung injury, as assessed by an increase in the lung wet to dry weight ratio, the presence of significant histopathological changes, such as perivascular edema and intravascular leukocyte aggregation, and an increase in the BAL fluid TNF-α concentration. These findings suggest that liver ischemia-reperfusion caused systemic inflammation, and that lung injury is triggered when high tidal volume ventilation follows liver ischemia-reperfusion.Adenovirus-mediated transfer of keratinocyte growth factor (KGF) cDNA successfully expressed high level of KGF in airway epithelial cells, and consequently raised significant lung epithelial cell proliferation, improved oxygenation, and decreased mortality. Furthermore, there was minimal vector-associated inflammation. We suggest that KGF gene transduction into lungs is a promising potential treatment for acute lung injury and would be a useful tool for regeneration research.

我们研究了麻醉和机械通气的大鼠，其中肝脏流入短暂中断两次，持续15分钟。两个潮气量，6 ml/kg（IR-LT）和24 ml/kg（IR-HT），在肝脏缺血-再灌注后，以及假手术后（NC-LT和NC-HT，分别）进行了评估。在4组中，仅IR-HT组发生肺损伤，通过肺湿干重比增加、存在显著组织病理学变化（如血管周围水肿和血管内白细胞聚集）以及BAL液TNF-α浓度增加进行评估。结果提示，肝缺血再灌注后，肺组织炎症反应明显，肺组织损伤可能是由高潮气量通气引起的，腺病毒介导的角质细胞生长因子（KGF）基因转染可使气道上皮细胞高表达KGF，从而促进肺上皮细胞增殖，改善氧合，降低死亡率。此外，存在最小的载体相关炎症。我们认为，KGF基因转导入肺是一个有前途的潜在治疗急性肺损伤，并将是一个有用的工具，再生研究。

项目成果

Keratinocyte growth factor gene transduction ameliorates acute lung injury and mortality in mice

• DOI: 10.1089/hum.2006.137
• 发表时间: 2007-02-01
• 期刊: HUMAN GENE THERAPY
• 影响因子: 4.2
• 作者: Baba, Yasuko;Yazawa, Takuya;Kurahashi, Kiyoyasu
• 通讯作者: Kurahashi, Kiyoyasu

High tidal volume ventilation induces lung injury after hepatic ischemia-reperfusion

• DOI: 10.1152/ajplung.00151.2006
• 发表时间: 2007-03-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
• 影响因子: 4.9
• 作者: Ota, Shuhei;Nakamura, Kyota;Kurahashi, Kiyoyasu
• 通讯作者: Kurahashi, Kiyoyasu