| Project/Area Number |
17390210
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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 |
General internal medicine (including Psychosomatic medicine)
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| Research Institution | Kyushu University |
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Principal Investigator |
SUDO Nobuyuki Kyushu University, Graduate School of Medical Sciences, Associate Professor (60304812)
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| Co-Investigator(Kenkyū-buntansha) |
NAGANO Jun KYUSHU UNIVERSITY, Institute of Health Science, Associate Professor (10325483)
KUBO Chiharu KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor (80117100)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,900,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2007: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2006: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | Psychosocial stress / brain-liver interaction / chronic hepatitis C / Apoptosis / prospective cohort study / disease-prone personality / 前向きコホート研究 / 疾患親和性性格 / 脳-肝相関 / C-型慢性肝炎 |
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| Research Abstract |
The main purpose of this study is to clarify whether or not stress can affect the severity and progression of liver diseases. To do this, we used the two different methodologies, such as basic study using animal models and epidemiological study on patients with chronic liver diseases.
In animal studies, we especially focused on the effect of the vagus nerve by using a selective hepatic vagotomy. To determine how the vagus nerve influences hepatocyte apoptosis, hepatitis was preceded by pretreatment with nicotine; PNU-282987, an α7 nicotinic acetylcholine receptor (AChR) agonist; liposome-encapsulated dichloromethylene diphosphonate (lipo-C12MDP), a macrophage eliminator; and Mn (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP), an oxidative inhibitor. As a result, mortality in the vagotomized mice was significantly higher than that in the sham-operated mice following intravenous administration with the anti-Fas antibody Jo-2. This result was also supported by the data from bot
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h terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling and caspase-3 assay, in which vagotomized livers showed a significant elevation in the number of apoptotic hepatocytes and increased caspase-3 activity following Jo-2 treatment compared with the sham-operated livers. Supplementation with nicotine and PNU-282987 dose dependently inhibited this detrimental effect of the vagotomy. Moreover, the vagotomy-triggered exacerbation of Fas-induced hepatitis was completely blocked by lipo-C12MDP. Similarly, pretreatment with MnTBAP also completely suppressed the vagotomy-triggered exacerbation. These results thus suggest that the hepatic vagus nerve could play an important role in attenuating Fas-induced hepatocyte apoptosis through α7 nicotinic AChR, perhaps by causing the Kupffer cells to reduce their generation of an excessive amount of reactive oxygen species.
Next our question is whether or not psychosocial stress increase the incidence of hepatocellular carcinoma in patients suffering from chronic hepatitis C. To clarify this, we set up the 5-years-prospective study in two hospitals of Fukuoka prefecture. In a cross-sectional analysis on the baseline data of 364 patients registered, no significant impact of psychosocial factors on the severity of liver diseases was evident. The follow-up will be completed by the end of 2008. We will be able to present the details of such results in the near future. Less
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