Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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Research Abstract |
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.
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