2004 Fiscal Year Final Research Report Summary
Development of synthetic surfactant and its protective effect on alveolar type II cell
| Project/Area Number |
15591621
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Kanazawa University |
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Principal Investigator |
TASHIRO Katsumi Kanazawa University, Graduate School of Medicine, Department of Anesthesiology and Intensive Care Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (30242556)
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| Project Period (FY) |
2003 – 2004
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| Keywords | surfactant protein / E.coli / alveolar type II cell / surfactant inhibition / ischemia reperfusion injury / inflammation / nicotine amide / alveoli |
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| Research Abstract |
(1)Development of a synthetic surfactant protein. A synthetic peptide mimicking surfactant protein-C (Sp-C) was expressed in E.coli, by using pET80 vector and synthetic DNA. However, the yield of synthetic peptide was extremely low. Next, we tried to express the synthetic peptide as fusion proteins fused with DHPP protein using pQE40 vector and with tluoredoxin using pET32a. However, the yields were low in both cases. The low yield is thought to be because of high toxicity of the synthetic peptide to E.coli. So, we could not succeed in expressing synthetic peptide.
(2)Protective of effect of hypercapnia. High concentration of carbon dioxide (suppressed the increase of TNF released from alveolar type II cell stimulated by IL-1 under cell culture. The levels of mRNA for inflammatory cytokine were not elevated. So, high concentration of carbon dioxide inhibits TNF release at the post-transcription level.
(3)Effect of nicotine amide of lung ischemia rperfuusion injury. The left lung of adult rats was reperfirsed after 90 min of ischemia. The arterial oxygen pressure of rats given nicotinamide was 290±80 (SD) mmHg and was significantly higher than that of the control rat (about 100 mmHg). Nicotine amide significantly reduced the lung ischemia reperfusion injury.
(4)Analysis of the lung expansion after surfactant impairment. Mechanical ventilation of immature newborn rabbits treated with surfactant mixed with serum causes the collapse of small alveoli and the overexpansion of large alveoli. However, this surfactant increased the tidal volume to the same extent as normal surfactant. Normal tidal volume dose not necessarily mean normal surfactant function and may lead to overlooking impaired surfactant function.
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