| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Kahoru KOBE UNIV. SCH. MED., DEPT. OF ANESTHESIOLOGY, INSTRUCTOR, 医学部, 助手 (20311780)
MIKAWA Katsuya KOBE UNIV. SCH. MED., DEPT. OF ANESTHESIOLOGY, ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (40229662)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
[Study 1] In acute lung injury, alveolar and airway epithelial cells are target for insult. On the other hand, the epithelium plays an important role in the pathogenesis of acute lung injury by producing various mediators and growth factors. The aim of the current study was to elucidate mediators produced by the epithelium and assess the effects of various drugs on mediators. Acute lung injury was induced by intraperitoneal endotoxin (10 mg/kg) in rats. Protein expression of inducible nitric oxide synthase (iNOS), nitrotyrosine (nTyr), tumor necrosis factor-α (TNF-α), and growth regulated oncogene (GRO/CINC) was immunohistochemically evaluated. Acute lung injury was quantified by lung wet/dry weight ratio and neutrophil counts in bronchoalveolar lavage fluid (BALF). The effects of lidocaine (2 mg/kg/hr), ketamine (10 mg/kg/hr), and propofol (20 mg/kg/hr) were assessed. Protein expression of iNOS, nTyr, and GRO/CINC was observed in alveolar type II pneumocytes 3-6 hr after endotoxin. Li
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docaine, ketamine, and propofol attenuated expression of these proteins. These drugs also attenuated increase in lung wet/dry weight ratio and neutrophils in BALF found in endotoxin-treated rats.
[Study 2] In process of recovery from acute lung injury and prevention of pulmonary fibrosis, proliferation of type II pneumocytes is a prerequisite. Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are well known to promote proliferation of the type II cells. The aim of the current study was to assess the effects of various drugs on proliferation of alveolar type II epithelial cells. Type II pneumocytes were isolated from rats' lungs and cultured. We assessed the effects of ketamine, lidocaine, and rolipram, a selective inhibitor of the type IV phosphodiesterase 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. Less
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