| Project/Area Number |
09670630
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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 |
Respiratory organ internal medicine
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| Research Institution | Tokai University |
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Principal Investigator |
TSUJI Chizuko Tokai University School of Medicine Assistant Professor, 医学部, 講師 (80130079)
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| Co-Investigator(Kenkyū-buntansha) |
HIROTA Yuki Hasumi Electro-Chemical and Cancer Institute Instructor, 助手
TANIGAKI Toshimori Tokai University School of Medicine Assistant Professor, 医学部, 講師 (90246091)
SHIOYA Sumie Tokai University School of Medicine Associate Professor, 医学部, 助教授 (20102840)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Nitric Oxide / Radiation Pneumonitis / inducible Nitric Oxide synthase (iNOS) / Aminoguanidine / Nitrotyrosine / Radiation / Acute Lung Injury / 肺傷害 |
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| Research Abstract |
The purpose of this study is to elucidate the role of nitric oxide in radiation-induced acute lung injury. We investigated the expression of nitric oxide synthase (NOS) mRNA, formation of nitrotyrosme and effect of NOS inhibitor m radiation-induced lung injury model. Wistar rats were divided into following 4 groups, 1) and untreated control group (C group), 2) irradiated group (R group), 3) aminoguanidine (AG), partially specific inhibitor of iNOS, treated group receiving the same dose of irradiation (R+AG group), 4) an aminoguanidine treated control group (AG group). The rats in R and R+AG groups were irradiated with 2OGy of ^<60>Co in one fraction to the left hemithorax. The rats in R+AG and AG groups were treated with aminoguanidine 2 hours before irradiation (in R+AG group) followed by daily subcutaneous injection of 50mg/kg along with oral administration of 2g/l aminoguanidine in drinking water. The experiments were done within 2 weeks after irradiation, acute stage of radiation i
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njury The expression of iNOS and endothehal NOS (ecNOS) mRNA measured with reverse transcriptase polymerase chain reaction (RT-PCR) method. The nitrotyrosine formation was measured by HPLC in tissue homogenate and was evaluated with immuno-stain in paraffin-embedded lung sections. The lung injury was evaluated with protein and LDH concentrations in bronchoalveolar lavage fluid and nuclear magnetic resonance spin-spin relaxation time T_2 of lung tissue. The concentration of protein and LDH increased and relaxation time T_2 prolonged in R group. The expression of iNOS and ecNOS mRNA increased in R group. We detected increase in nitrotyrosine formation in R group. Nitrotyrosine positive cells were alveolar epithelial cells and alveolar macrophages. Nitrotyrosine positive aria had tendency to agree with injury. In R+AG group, the formation of nitrotyrosine was attenuated and increase in concentration of protein and LDH and the prolongation of relaxation time T2 were prevented. The results indicated that excess nitric oxide played a sigraficant role in pathogenesis of acute stage of radiation-induced lung injury via formation of nitrotyrosme. Less
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