| Project/Area Number |
22591595
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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 |
Cerebral neurosurgery
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
MIZUNO Toshiki 京都府立医科大学, 大学院・医学研究科, 准教授 (30264782)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATA Tetsuo 京都薬科大学, 薬学部, 教授 (30237292)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | TGF β / 脳小血管病変 / 高血圧モデルラット / TGFβ / 脳小血管病 / 脳腎連関 |
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| Research Abstract |
CARASIL is caused by the mutation n the serine protease HTRA1, which regulates transforming growth factor-β (TGF-beta 1) signaling. The pathological feature of CARASIL is arteriosclerosis with intimal thickening and dense collagen fibers, loss of vascular smooth-muscle cells, and hyaline degeneration of the tunica media in cerebral small arteries, which resembles nonhereditary cerebral small-vessel disease. While TGF-beta 1 plays a key role in the maintenance of normal blood vessel wall structure, the contribution of TGF-beta to the development of atherosclerosis is obscure. We examined TGF-beta 1 in rat removing unilateral kidney and overloading deoxycorticosterone（DOCA）and salt to clarify a role of TGF-beta 1 in the hypertensive brain and kidney. After unilateral kidney was removed, DOCA and 1% NaCl were administrated to a rat for 3 or4 weeks（DOCA-salt）. Systolic blood pressure (SBP) and heart rates (HR) in the rat were measured once a week by tail cuff method. After measuring mean arterial blood pressure (MAP) and HR by a cannula from inguinal artery invasively, kidney, aorta, cerebral artery and brain were removed. TGF -beta 1 in each organ was measured by ELISA and western blotting.SBP and MAP in the rat with DOCA-salt significantly increased during the course. TGF bera1 increased from 0.06 ± 0.005 ng/mg to 0.16 ± 0.012 ng/mg in the kidney, from 0.59 ± 0.07 ng/mg to 2.64 ± 0.45 ng/mg in the aorta after 3 weeks. While TGF bera1 did not change significantly from 0.019 ± 0.004 ng/mg to 0.022 ± 0.003 ng/mg after 3 weeks, but it increased significantly after 4 weeks in the cervical artery and the brain.The increase of the TGF bera1 in the kidney and the aorta precedes the increase of the TGF bera1 in the cervical artery and the brain.
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