1995 Fiscal Year Final Research Report Summary
Studies on Pathogenesis of Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis
| Project/Area Number |
05670507
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Kurume University School of Medicine |
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Principal Investigator |
SAKISAKA Shotaro Kurume University School of Medicine, 2nd Department of Medicine, Assistant Prof., 医学部, 講師 (90158923)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Masaru Kurume University School of Medicine, 2nd Department of Medicine, Assistant, 医学部, 助手 (00241175)
SHAKADO Satoshi Kurume University School of Medicine, 2nd Department of Medicine, Assistant, 医学部, 助手 (80241181)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Primary Biliary Cirrhosis / Primary Sclerosing Cholangitis / Heat Shock Protein / Endotoxin / Blind Loop / Immunohistochemistry / Cultured biliary epithelial cells |
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| Research Abstract |
1. To investigate pathogenesis of primary sclerosing cholangitis (PSC), an animal model of PSC was made in rats by making a 10 cm blind loop. Eight weeks after the operation, marked fibrosis was observed around the intra- and extra-hepatic bile ducts. Retrograde cholangiogram revealed dilatation and narrowing of the intra- and extra-hepatic bile ducts. These rat models showed high incidence of portal blood endotoxemia compared the one in control rats. Immunohistochemistry using anti-LPS (endotoxin) antibody demonstrated the localization of endotoxin in BECs of intra- and extra-hepatic bile ducts. These findings suggested that we could make the animal model which showed morphological features quite similar to those of PSC patients, and endotoxin absorbed from the blind loop may play an important role in the pathogenesis of this model as well as of PSC.
2. To investigate pathogenesis of primary biliary cirrhosis (PBC), western blotting, in situ hybridization, and immunohistochemistry for heat shock proteins (HSPs) using anti-HSP antibodies were performed with biopsied livers from PBC patient. In the PBC liver, expression of HSPs was increased markedly in BECs and moderately in hepatocytes compared the one in the liver of controls, chronic hepatitis type C,and PSC.Expression of HSPs in the PBC liver was significantly reduced after treatment with ursodeoxycholic acid (UDCA), most effective therapeutic drug for PBC,and significant correlation was observed between improvement of serum liver function tests and reduction of hepatic HSP expression after UDCA treatment.
3. Biliary epithelial cells (BEC) were isolated from rat and guinea pig and their morphology and physiology were observed as the preliminary study for observing reactions between isolated human BEC from a resected liver and serum or lymphocytes from patients with PBC or PSC.
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Research Products
(26 results)
