Regenerative therapy for acute lung injury based on intercellular cross talk

基于细胞间串扰的急性肺损伤再生治疗

• 批准号: 14370489
• 负责人: OBARA Hidefumi
• 金额: $ 4.86万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370489/
• 关键词: Acute lung injury; Apoptosis; Alveolar epithelial cells; Phosphodiesterase inhibitors; Bleomycin; Endotoxin; Endothelial progenitor cells; Neutrophils; 血管内皮前駆細胞; プレオマイシン

Regenerative therapy for acute lung injury consists of proliferation and repairment of alveolar epithelial and epithelial cells, and [3] prevention of lung fibrosis.CD34-positive cells were isolated from peripheral blood, and were differentiated to epithelial progenitor cells using EBM-2 medium containing VEGF, FBS, and IGF. In bleomycin-induced lung injury but not endotoxin-induced lung damage, blood microvessels were proliferated. The effects of rolipram (PDE-IV inhibitor) on proliferation of alveolar type II pneumocytes (AEC-II). Rolipram increased spontaneous proliperation and enhanced KGF/HGF-induced proliferation. Immunohistochemical analysis using BrdU antibody revealed that rolipram increased DNA synthesis in type II pneumocytes in mice treated with KGF/HGE. Acute lung injury was induced by intraperitoneal endotoxin in mice. Rolipram attenuated the morphological damages of the lung injury. We also biochemically and pathologically investigated whether exogenous intratracheal instillation of AEC-II isolated from rats can prevent fibrotic changes in endotoxin-induced lung injury. Intratracheal administration of AEC-II cells attenuated damage of epithelial cells and alveolar fibrosis although not significantly.

急性肺损伤的再生治疗包括肺泡上皮和上皮细胞的增殖和修复，以及[3]预防肺纤维化。从外周血中分离CD34阳性细胞，并在含有VEGF、FBS和IGF的EBM-2培养液中分化为上皮祖细胞。在博莱霉素性肺损伤而非内毒素肺损伤中，微血管增殖。罗利普兰(PDE-IV抑制剂)对肺泡II型上皮细胞增殖的影响罗利普兰增加自发性增殖，增强KGF/HGF诱导的增殖。BrdU抗体的免疫组织化学分析显示，罗利普兰增加了KGF/HGE处理的小鼠II型肺泡细胞的DNA合成。采用小鼠腹膜内毒素致急性肺损伤模型。罗利普兰可减轻肺损伤的形态损害。我们还从生化和病理角度研究了从大鼠气管内注入外源性AEC-II是否可以预防内毒素诱导的肺损伤的纤维化改变。气管内注射AEC-II细胞可减轻上皮细胞的损伤和肺泡纤维化，但不显着。

项目成果

Nishina K: "Effects of Intravenous Anesthetics and Lidocaine of Proliferation of Cultured Type II Pneumocytes and Lung Fibroblasts"Anesthesia & Analgesia. 94(2). 385-388 (2002)

Nishina K：“静脉麻醉药和利多卡因对培养的 II 型肺细胞和肺成纤维细胞增殖的影响”麻醉

ARDSの治療 サーファクタント補充療法

ARDS 的治疗 表面活性剂替代疗法

• 发表时间: 2004
• 期刊: 医学のあゆみ 別冊
• 作者: Kadoi Y;Goto F.;尾原 秀史
• 通讯作者: 尾原 秀史

森川 修: "急性肺傷害の病態と治療"臨床麻酔. 26(増刊). 339-353 (2002)

Osamu Morikawa：“急性肺损伤的病理学和治疗”临床麻醉 26（特别版）。

The effects of intravenous anesthetics and lidocaine on proliferation of cultured type II pneumocytes and lung fibroblasts.

静脉麻醉药和利多卡因对培养的 II 型肺细胞和肺成纤维细胞增殖的影响。

• 发表时间: 2002
• 期刊: Anesthesia & Analgesia 94-2
• 作者: Nishina;Kahoru
• 通讯作者: Kahoru

Efficacy of partial liquid ventilation in improving acute lung injury induced by intratracheal acidified infant formula: Determination of optimal dose and positive end-expiratory pressure level

• DOI: 10.1097/01.ccm.0000104954.22016.d2
• 发表时间: 2004-01-01
• 期刊: CRITICAL CARE MEDICINE
• 影响因子: 8.8
• 作者: Mikawa, K;Nishina, K;Obara, H
• 通讯作者: Obara, H