The effect of insulin-like growth factor-I on hepatocyte apoptosis after bile duct ligation in rat

Shyr Ming Sheen-Chen, Hsin Tsung Ho, Lu Chia-Pei, Kuo Sheng Hung, Hock Liew Eng

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Obstructive jaundice may promote bacterial overgrowth and altered intestinal barrier function, with resultant increased translocation of endotoxin to the liver, amd thus may potentiate the phenomenon of hepatocyte apoptosis. Exogenous administration of insulin-like growth factor-I (IGF-I) has been shown to enhance mucosal adaptation after small bowel resection in rats and also to accelerate repair of small intestinal mucosa after damage by the chemotherapy drug methotrexate. The aim of the current study was to determine the effect of exogenous IGF-I administration on hepatocyte apoptosis after bile duct ligation in rat. Male Sprague-Dawley rats weighing 250-300 g were randomized to three groups (n=6 in each group). Group 1 (control; C) underwent sham operation and was simultaneously treated with the same amount of normal saline. Group 2 (obstructive jaundice; OB) underwent common bile duct ligation without other manipulation. Group 3 (obstructive jaundice with IGF-I; OBIGF-I) underwent common bile duct ligation and simultaneous treatment with recombinant human IGF-I (a total dose of 1 mg in each rat, divided into six administrations; about 1 mg/kg/day). After 3 days, liver tissue was harvested and immediately snap-frozen in liquid nitrogen for histopathologic analysis and apoptosis measurements. Compared with the sham operation group (C), increased hepatocyte apoptosis (P <0.001) and ductular proliferation (P <0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P <0.001 and P <0.001, respectively). There was no significant difference in hepatocyte apoptosis (P=0.925) or ductular proliferation (P=0.385) between the sham control group (C) and the OBIGF-I group. Increased hepatocyte apoptosis (P <0.001) and ductular proliferation (P <0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P <0.001 and P <0.001, respectively).

Original languageEnglish
Pages (from-to)2220-2224
Number of pages5
JournalDigestive Diseases and Sciences
Volume51
Issue number12
DOIs
Publication statusPublished - Dec 2006
Externally publishedYes

Keywords

  • Bile duct ligation
  • Hepatocyte apoptosis
  • Insulin-like growth factor-I

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

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