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THERAPY FOR ACUTE LUNG INJURY : TARGET FOR TYPE II ALVEOLAR EPITHELIAL CELLS

急性肺损伤的治疗：针对 II 型肺泡上皮细胞

基本信息

批准号：
11671496
负责人：
MIKAWA Katsuya
金额：
$ 2.3万
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：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671496/
关键词：
HGF KGF ALVEOLAR EPITHELIUM ARDS ROLIPRAM KETAMINE LIDOCAINE APOPTOSIS

项目摘要

In process of recovery from acute lung injury and prevention of pulmonary fibrosis, proliferation of type II alveolar epithelial cells is a prerequisite. In the current study, we mainly assessed the effects of rolipram, a PDE-IV inhibitor, and anesthetics (propofol, midazolam, ketamine, and lidocaine) on the type II cells proliferation and apoptosis. (1) Type II pneumocytes were isolated from rats' lungs and cultured. We assessed the effects of ketamine, lidocaine, midazolam, propofol, and rolipram on proliferation of type II cells in the presence and absence of KGF or HGF.Ketamine and lidocaine had no effect. These drugs failed to enhance KGF/HGF-induced promotion of type II cell proliferation. Rolipram successfully enhanced proliferation of type II pneumocytes in the absence of the growth factors, and furthermore increased enhancement of type II cells proliferation by KGF/HGF.BrdU uptake by the type II cells was increased in the lung of mice receiving intraperitoneal rolipram. (2) Rolipram, propofol, midazolam, ketamine, and lidocaine had no effect on proliferation of cultured fibroblasts (JTC-19). (3) Rolipram increased expression SP-B mRNA in cultured type II cells as evidenced by Northern blotting. (4) In rats, pretreatment with these drugs successfully attenuated pathological and biochemical changes in acute lung injury induced by endotoxin.

在急性肺损伤的恢复和预防肺纤维化的过程中，II型肺泡上皮细胞的增殖是先决条件。在本研究中，我们主要评估了PDE-IV抑制剂咯利普兰和麻醉药（丙泊酚、咪达唑仑、氯胺酮和利多卡因）对II型细胞增殖和凋亡的影响。 (1)从大鼠肺中分离并培养II型肺细胞。我们评估了在存在和不存在 KGF 或 HGF 的情况下氯胺酮、利多卡因、咪达唑仑、异丙酚和咯利普兰对 II 型细胞增殖的影响。氯胺酮和利多卡因没有影响。这些药物未能增强 KGF/HGF 诱导的 II 型细胞增殖促进作用。在没有生长因子的情况下，咯利普兰成功地增强了 II 型肺细胞的增殖，并且进一步增加了 KGF/HGF 对 II 型细胞增殖的增强作用。接受腹腔内咯利普兰的小鼠的肺中 II 型细胞对 BrdU 的摄取增加。 (2)咯利普兰、丙泊酚、咪达唑仑、氯胺酮和利多卡因对培养的成纤维细胞(JTC-19)的增殖没有影响。 (3) 咯利普兰增加了培养的 II 型细胞中 SP-B mRNA 的表达，如 Northern 印迹所证明。 (4)在大鼠中，这些药物的预处理成功地减轻了内毒素引起的急性肺损伤的病理和生化变化。