| Project/Area Number |
14571261
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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 |
Thoracic surgery
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| Research Institution | Mie University |
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Principal Investigator |
SHIMPO Hideto Mie University, Faculty of Medicine, Professor, 医学部, 教授 (70179076)
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| Co-Investigator(Kenkyū-buntansha) |
MITANI Yoshihide Mie University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (60273380)
矢田 公 三重大学, 医学部, 教授 (80093152)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | pulmonary hypertension / p38MAPK / inflammation / remodeling of pulmonary artery / 肺血管再構築 / P38MAPK |
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| Research Abstract |
We postulated that inhibition of p38 MAPK with FR 167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats. Rats were divided into four groups : the control group, FR group (daily FR 167653), MCT group (60mg/kg monocrotaline), MCT with FR group (daily FR 167653 after single MCT).
Four weeks after monocrotaline administration, mean pulmonary artery pressure in the MCT with FR group was lower than in the MCT group. In morphometric analysis the percentage of medial wall thickness and percentage of muscularization in the MCT with FR group were reduced compared with those in the MCT group. P38MAPK activity was significantly attenuated in the MCT with FR group compared with in the MCT group. mRNA levels of tumor necrosis factor α and interleukin 1β were reduced in the MCT with FR group compared with in the MCT group.
Fr-167653 significantly attenuates the expression of cytokines, ultimately preventing the progression of pulmonary hypertension. These results suggest that p38MAPK might play a center role of in the molecular events that underline the development and progression of pulmonary hypertension.
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