期刊
JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
卷 23, 期 5, 页码 260-269出版社
WILEY
DOI: 10.1002/jhbp.333
关键词
Glutathione peroxidase; Liver fibrosis; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Oxidative stress; Superoxide dismutase
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
BackgroundWe previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. MethodsEight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. ResultsAfter 5weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. ConclusionHypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress.
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