期刊
MEDICAL MOLECULAR MORPHOLOGY
卷 43, 期 3, 页码 134-138出版社
SPRINGER TOKYO
DOI: 10.1007/s00795-009-0480-9
关键词
Primary biliary cirrhosis; Sodium taurocholate cotransporting polypeptide; Hepatic cholesterol 7 alpha-hydroxylase; Bile salt export pump; End-stage liver disease
资金
- Intractable Liver Disease Foundation of the Japanese Ministry of Health, Labour and Welfare
- Clinical Research Foundation [2009-03]
- Department of Gastroenterology and Medicine, Fukuoka University
To examine the mRNA expression of hepatobiliary transporters in primary biliary cirrhosis (PBC) patients and to compare bile acid absorption, synthesis, and efflux in patients with non-end-stage and end-stage PBC, we obtained liver samples from PBC patients by percutaneous needle biopsy. End-stage PBC was defined as follows: histological stage IV; cirrhosis; serum total bilirubin, a parts per thousand yen4.0 mg/dl; and Child-Pugh Class C. The mRNA expression levels of sodium taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), and hepatic cholesterol 7 alpha-hydroxylase (CYP7A1) were significantly higher in the PBC patients than in the controls (P < 0.01). The mRNA levels of NTCP and BSEP were significantly higher in the end-stage PBC patients than in the controls (P < 0.01). However, hepatic CYP7A1 mRNA expression decreased significantly (by 70%) in the patients with end-stage PBC as compared to the controls and the patients with non-end-stage PBC (P < 0.01). The hepatic expression of transporters mediating bile acid influx and efflux showed sustained elevation, whereas that of the rate-limiting enzyme for bile acid biosynthesis was attenuated in the end-stage PBC patients. Thus, mechanisms may be present preventing the accumulation of toxic bile acids in the hepatocytes of end-stage PBC patients.
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