| Project/Area Number |
26293284
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
柳川 徹 筑波大学, 医学医療系, 准教授 (10312852)
酒井 俊 筑波大学, 医学医療系, 講師 (30282362)
磯辺 智範 筑波大学, 医学医療系, 准教授 (70383643)
蕨 栄治 筑波大学, 医学医療系, 講師 (70396612)
正田 純一 筑波大学, 医学医療系, 教授 (90241827)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | 脂肪性肝炎 / 生活習慣病 / LPS / 歯周病菌 / 腸内細菌 / 非アルコール性脂肪性肝炎 / Kupffer細胞 / 歯周病 / 転写因子 / 酸化ストレス / 遺伝子改変マウス / 運動 / 口腔内環境 / 脂肪性肝疾患 / 運動療法 |
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| Outline of Final Research Achievements |
It has been reported that the onset mechanism of NASH is associated with abnormal intestinal bacterial flora, infection of periodontal disease bacteria, and its related increase in LPS influx into the liver. p62:Nrf2 gene double knockout mice (DKO) spontaneously develop NASH. Therefore, DKO was studied in terms of the abnormalities of intestinal bacterial flora and intestinal barrier function. In vivo analysis, the serum and fecal LPS concentrations were increased in DKO. In the intestinal microflora, the number of gram-negative bacteria species was increased in DKO. The intestinal permeability was increased in DKO. In vitro analysis, the cellular membrane resistance value and tight junction protein expression levels were decreased in the Nrf2-deficient intestinal cells. It is likely that the onset mechanism of NASH is attributed to an increase in gram-negative bacteria species and a weakness of intestinal barrier function.
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