THERAPY FOR ACUTE LUNG INJURY WITH PROLIFERATION OF TYPE II PNEUMOCYTES AND REGULATION OF APOPTOSIS OF INFLAMMATORY

伴有 II 型肺细胞增殖和炎症细胞凋亡调节的急性肺损伤的治疗

• 批准号: 12671467
• 负责人: NISHINA Kahoru
• 金额: $ 1.73万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671467/
• 关键词: ACUTE LUNG INJURY; APOPTOSIS; REGENERATIVE MEDICINE; INFLAMMATORY CELLS; ALVEOLAR EPITHELIUM; PULMONARY FIBROSIS; GROWTH FACTOR; 急性肺傷害; 呼吸窮迫症候群; ケモカイン; 好中球; II型肺胞上皮細胞

Therapy for acute lung injury consists of [1] cessation of alveolar inflammation, [2] repairment of alveolar epithelium, and [3] prevention of lung fibrosis. We first investigated the effects of rolipram (PDE-IV inhibitor), lidocaine, midazolam, propofol, ketamine (anesthetics) on apoptosis of neutrophils and alveolar type II pneumocytes. Anti-Fas antibody-induced apoptosis of neutrophils was enhanced by rolipram and not by the anesthetics. Endotoxin-induced apoptosis of type II pneumocytes was inhibited by rolipram and propofol. We secodly assessed the effects of these drugs on proliferation of rat cultured type II pneumocytes. 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/HGF. Acute lung injury was induced by intraperitoneal endotoxin (10 mg/kg) in mice. Rolipram attenuated the pathological changes of the lung injury. This successful result of rolipram may be due to the effect of the drug on neutrophils and the alveolar epithelial cells.

急性肺损伤的治疗包括[1]停止肺泡炎症，[2]修复肺泡上皮，[3]预防肺纤维化。我们首先研究咯利普兰（PDE-IV抑制剂），利多卡因，咪达唑仑，异丙酚，氯胺酮（麻醉剂）对中性粒细胞和肺泡II型细胞凋亡的影响。抗Fas抗体诱导的中性粒细胞凋亡是由咯利普兰，而不是由麻醉剂增强。咯利普兰和丙泊酚可抑制内毒素诱导的肺Ⅱ型细胞凋亡。我们还观察了这些药物对培养的大鼠肺Ⅱ型细胞增殖的影响。Rolipram增加自发增殖和增强KGF/HGF诱导的增殖。BrdU抗体的免疫组织化学分析显示，咯利普兰增加了KGF/HGF处理的小鼠II型肺细胞的DNA合成。腹腔注射内毒素（10 mg/kg），造成小鼠急性肺损伤。咯利普兰可减轻肺损伤的病理改变。咯利普兰的这一成功结果可能是由于药物对中性粒细胞和肺泡上皮细胞的作用。

项目成果

K. Mikawa, K. Nishina, S. Kodama, et al: "Propofol attenuates sepsis-induced diahragmatic dysfunction in hamsters"Anesthesiology. 94. 652-660 (2001)

K. Mikawa、K. Nishina、S. Kodama 等人：“异丙酚可减轻仓鼠脓毒症引起的膈肌功能障碍”麻醉学。

Nishina K: "The effects of intravenous anesthetics and lidocaine on proliferation of cultured type II pneumocytes and lung fibroblas"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”麻醉与镇痛 94・2（2002）。

Y. Kiyonari, K. Nishina, K. Mikawa, et al: "Lidocaine attenuates acute lung injury induced by combination of phospholipase A2 and trypsin"Crit Care Med. 28. 489-489 (2000)

Y. Kiyonari、K. Nishina、K. Mikawa 等人：“利多卡因可减轻磷脂酶 A2 和胰蛋白酶组合诱导的急性肺损伤”Crit Care Med。

K. Mikawa, H. Akamatsu, K. Nishina, et al: "The effect of phosphodiesterase III inhibitors on human neutrophil function"Crit Care Med. 28. 1001-1005 (2000)

K. Mikawa、H. Akamatsu、K. Nishina 等人：“磷酸二酯酶 III 抑制剂对人类中性粒细胞功能的影响”Crit Care Med。

Nishikawa: "The effects of intravenous anesshctics and lidocaine on proliferaction of cultured type II pnemocytes and lung fibroblasts"Anestheria & Analgenia. 94・2. 385-388 (2002)

西川：“静脉麻醉剂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”Anestheria & Analgenia 94・2 (2002)。