The effect of insulin-like growth factor-I on hepatocyte apoptosis after bile duct ligation in rat.
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).
Sheen-Chen
Shyr-Ming
SM
Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. smsheen@yahoo.com
Ho
Hsin-Tsung
HT
Chia-Pei
Lu
L
Hung
Kuo-Sheng
KS
Eng
Hock-Liew
HL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001652:Bile Ducts / Q000503:physiopathology* / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use; D041781:Jaundice, Obstructive / Q000188:drug therapy; D008026:Ligation; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D007334:Insulin-Like Growth Factor I