| Project/Area Number |
02807079
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Shinshu University School of Medicine |
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Principal Investigator |
KUBO Keishi Shinshu Univ., Sch. of Med., Assistant Professor, 医学部, 講師 (80143965)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Akio Shinshu Univ., Sch. of Med., Associate Professor, 医学部附属心脈管研究施設, 助教授 (70020758)
UEDA Gou Shinshu Univ., Sch. of Med., Professor, 医学部附属心脈管研究施設, 教授 (10020702)
MATSUZAWA Yukinori Shinshu Univ., Sch. of Med., Assistant, 医学部附属病院, 助手 (40219423)
KOBAYASHI Toshio Shinshu Univ., Sch. of Med., Assistant Professor, 医学部附属病院, 講師 (80020775)
SEKIGUCHI Morie Shinshu Univ., Sch. of Med., Professor, 医学部, 教授 (70075232)
YOSHIMURA Kazuhiko Shinshu Univ., Sch. of Med., Assistant Professor (70174985)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Endotoxin / Lung injury / Tumor necrosis factor / Oxygen radicals / Sheep / ARDS / Superoxide dismutase / 慢性肺リンパ瘻 / superoxide dismutase / エンドトキシン肺損傷 / TNF肺損傷 / 肺循環動態 / 肺リンパ動態 / トロンボキサンA_2 / 好中球 / 動脈血ガス分析 |
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| Research Abstract |
In the present project we performed the two main studies to clarify the pathophysiology of endotoxin-induced lung injury using awake sheep with chronic lung lymph fistula. First study is to see the pathophysiology of TNF (tumor necrosis factor)-induced lung injury. After infusion of recombinant human TNF (r-hTNF) produced the almost same lung injuries as endotoxin-induced lung injury which we have reported^<1)>, such as the early pulmonary hypertension, transient leukopenia, decreased PaO_2 and the increased permeability pulmonary edema during the late phase. Pretreatment of selective thromboxane synthetase inhibitor, OKY-046, inhibited the early pulmonary hypertension induced by TNF, though other lung injuries did not change. Furthermore, the appearance of lung injuries induced by TNF occurred earlier 0.5-1hr than that induced by endotoxin. Secondly we examined the effects of recombinant human superoxide dismutase (r-hSOD) on endotoxin-induced lung injury to see the role of superoxide anion (O_2^-). Treatment of r-h SOD suppressed lung injuries as mentioned above, but the degree of inhibition was approximately half.
These results suggest that the mechanism of endotoxin-induced lung injury in awake sheep is complicated. O_2^- has an important role in this injury. However, we need to study the role of other oxygan radicals than O_2^- and some chemical mediators such as proteases. TNF infusion resulted in the same lung injury as that caused by endotoxin. Recently, intravascular macrophages (M*) are thought to have a central role in the development of endotoxin-induced lung injury. M* releases several mediators when stimulated by endotoxemia, and these mediators lead to lung injury. We need further studies to see whether TNF is crucial among these mediators.
( ^<1)> Kubo and Kobayashi : Am Rev Respir Dis 132 : 494, 1985)
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