2023 Fiscal Year Final Research Report
Endothelial nitric oxide synthase uncoupling cause lower urinary tract dysfunction associated with pelvic arterial occlusion
| Project/Area Number |
19K09675
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
秦 淳也 福島県立医科大学, 医学部, 助教 (00769606)
小島 祥敬 福島県立医科大学, 医学部, 教授 (60305539)
石橋 啓 福島県立医科大学, 医学部, 博士研究員 (90347211)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Keywords | 慢性膀胱虚血 / 下部尿路機能障害 |
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| Outline of Final Research Achievements |
This study divided male Sprague-Dawley rats into Control, chronic bladder ischemia (CBI) and CBI with oral BH4 supplementation (CBI/BH4) groups. In the CBI group, bladder capacity and bladder muscle strip contractility were lower, and arterial wall was thicker than in Controls. The improvements were seen in bladder capacity, muscle strip contractility and arterial wall thickening in the CBI/BH4 group as compared with the CBI group. Western blot analysis of bladder showed expressions of eNOS, HIF-1α and DHFR, which could regenerate BH4, were higher in the CBI group than in Controls. In the CBI/BH4 group, HIF-1α and DHFR expressions were decreased compared with the CBI group. Our results suggest that chronic ischemia increases eNOS and DHFR in the bladder to prevent atherosclerosis progression. However, DHFR could not synthesize sufficient BH4 relative to the increased eNOS, resulting in LUTD. BH4 supplementation protects lower urinary tract function by promoting eNOS activity.
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| Free Research Field |
下部尿路機能障害
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| Academic Significance and Societal Importance of the Research Achievements |
過活動膀胱の原疾患は多岐にわたるが、現在は病態を無視した対症療法が行われている。今後、病態に即した治療を行うことが求めらる。一方、酸化ストレス増加の要因として血管内皮における内皮型NOSアンカップリングが注目されている。eNOSの補酵素であるBH4が不足すると、eNOSによるNO合成が減少し、活性酸素の産生が増加する。この現象が内皮型NOSアンカップリングと呼ばれ、その増加した活性酸素は血管内皮を障害し動脈硬化を促進させる。今回、動脈硬化に起因する慢性虚血が引き起こす過活動膀胱と内皮型NOSアンカップリングの関連性を評価し、慢性虚血による過活動膀胱の発症機序に即した新規予防薬を探索すした。
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