| Project/Area Number |
15H04788
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene and public health
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| Research Institution | Chubu University |
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Principal Investigator |
NASU Tamie 中部大学, 生命健康科学部, 特任教授 (10020794)
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| Co-Investigator(Kenkyū-buntansha) |
石井 晃 名古屋大学, 医学系研究科, 教授 (30252175)
内藤 久雄 藤田保健衛生大学, 医学部, 講師 (90547556)
山ノ下 理 中部大学, 生命健康科学部, 講師 (50424924)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | NASH / コレステロール / 高血圧 / 降圧剤 / 線維症 / CD68 / SHR / TNFα / 非アルコール性脂肪性肝炎 / 血圧 / 高脂肪食 / 胆汁酸 / 相互作用 / ヒドララジン / 高脂肪-高コレステロール食 / 線維化 / コラーゲン / 炎症 / 予防 / Wistar-Kyoto / SHRSP5/Dmcr |
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| Outline of Final Research Achievements |
We investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in HFC diet-induced NASH among hypertensive SHR and SHRSP5/Dmcr, and normotensive WKY. The diet induced severe NASH in the hypertensive rats, whereas it only caused mild NASH in the normotensive rats. Increased activation of TGFβ/MAPK pathway was observed in the hypertensive rats; it suppressed nrf2 pathway in the hypertensive rats and led to lower increases in the hepatic level of HO-1. These signaling pathways might play crucial roles in the development of hypertension-associated NASH.
We also investigated whether antihypertensive drug suppress HFC-induced NASH in hypertensive SHR rats. It suppressed HFC-induced NASH in the liver of SHR rats. It significantly suppressed HFC-induced increases of inflammation- and fibrosis-related molecular markers. Thus, intervention of antihypertensive drug might be important in the prevention of NASH.
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