Digestive Diseases and Sciences

, Volume 51, Issue 12, pp 2220–2224 | Cite as

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
Original paper
First Online:
Received:
Accepted:

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).

Key words

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

Acknowledgment

This work was supported by Grant NSC 92-2314-B-182A-150 from the National Science Council of the Republic of China.

References

  1. 1.
    Pitt HA, Cameron JL, Postier RG, Gadacz TR (1981) Factor affecting mortality in biliary tract surgery. Am J Surg 141:66–72CrossRefPubMedGoogle Scholar
  2. 2.
    Su CH, Peng FK, Lui WY (1992) Factors affecting morbidity and mortality in biliary tract surgery. World J Surg 16:536–540CrossRefPubMedGoogle Scholar
  3. 3.
    Deitch EA, Sitting K, Berg R, Spegaw RD (1990) Obstructive jaundice promotes bacterial translocation from the gut. Am J Surg 159:79–87CrossRefPubMedGoogle Scholar
  4. 4.
    Bossuyt HV, Desmaretz C, Gaeta GB, Wisse E (1990) The role of bile acids in the development of endotoxemia during obstructive jaundice in the rat. J Hepatol 10:274–279CrossRefPubMedGoogle Scholar
  5. 5.
    Sheen-Chen SM, Chau PHW (1998) Obstructive jaundice alters Kupffer cell function independent of bacterial translocation. J Surg Res 80:205–209CrossRefPubMedGoogle Scholar
  6. 6.
    Moazzam FN, Brems JJ, Yong SL, et al. (2002) Endotoxin potentiates hepatocyte apoptosis in cholestass. J Am Coll Surg 194:731–739CrossRefPubMedGoogle Scholar
  7. 7.
    Patel T, Bronk SF, Gotes GJ (1994) Increase of intracellular magnesium promotes glycodeoxycholate-induced apoptosis in rat hepatocyte. J Clin Invest 94:2183–2192PubMedCrossRefGoogle Scholar
  8. 8.
    Kaiserlian D, Vidal K (1993) Antigen presentation by intestinal epithelial cells. Immunol Today 14:144CrossRefPubMedGoogle Scholar
  9. 9.
    Arnaiz-Villena, Perez-Blas M, Corell A, et al. (1997) Cell surface phenotype ultramicroscopic analysis of purified human enterocytes: a possible antigen-presenting cell in the intestine. Tissue Antigens 50:586–592PubMedCrossRefGoogle Scholar
  10. 10.
    Marin ML, Green Stein AJ, Geller SA, et al. (1983) A freeze fracture study of Crohn's disease of the terminal ileum: Changes in epithelial light junction organization. Am J Gastroenterol 78:537–547PubMedGoogle Scholar
  11. 11.
    Jones JI, Clemmons DR (1995) Insulin-like growth factors and their binding proteins: Biological actions. Endocr Rev 16:3–34CrossRefPubMedGoogle Scholar
  12. 12.
    Le Roith D (1997) Insulin-like growth factors. N Engl J Med 336:633–640CrossRefPubMedGoogle Scholar
  13. 13.
    Vanderhoof JA, McCusker RH, Clark R, et al. (1992) Truncated and native insulin-like growth factor I enhance mucosal adaptation after jejunoileal resection. Gastroenterology 102:1949PubMedGoogle Scholar
  14. 14.
    Howarth GS, Penning KA, Cool JC, et al. (1994) IGF-I and repair of the methotrexate damaged small intestine. Growth Reg 4:1204 [abstract]Google Scholar
  15. 15.
    Sheen-Chen SM, Chau P, Harris HW (1998) Obstructive jaundice alters Kupffer cell function independent of bacterial translocation. J Surg Res 80(2):205–209CrossRefPubMedGoogle Scholar
  16. 16.
    Sheen-Chen SM, Chen HS, Ho HT, Chen WJ, Sheen CC, Eng HL (2002) Effect of bile acid replacement on endotoxin-induced tumor necrosis factor-alpha production in obstructive jaundice. World J Surg 26:448–450CrossRefPubMedGoogle Scholar
  17. 17.
    Sheen-Chen SM, Ho HT, Chen WJ, et al. (2002) Obstructive jaundice alters CD44 expression in rat small intestine. Digestion 65:112–117CrossRefPubMedGoogle Scholar
  18. 18.
    Sheen-Chen SM, Chen HS, Ho HT, et al. (2003) Obstructive jaundice alters LFA-1 alpha expression in rat small intestine. Dig Dis Sci 48:1165–1170CrossRefPubMedGoogle Scholar
  19. 19.
    Sheen-Chen SM, Ho HT, et al. (2003) Obstructive jaundice alters proliferating cell nuclear antigen expression in rat small intestine. World J Surg 27:1161–1164CrossRefPubMedGoogle Scholar
  20. 20.
    Miyoshi H, Rust C, Roberts PJ, et al. (1999) Hepatocyte apoptosis after bile duct ligation in the mouse involves Fas. Gastroenterology 117:669–677CrossRefPubMedGoogle Scholar
  21. 21.
    Steeb CB, Trahair JF, Tomas FM, et al. (1994) Prolonged adminstration of IGF peptide enhances growth of gastrointestinal tissue in normal rats. Am J Physiol 266:G1090–G1098PubMedGoogle Scholar
  22. 22.
    Read LC,Tomas FM, Howarth GS, et al. (1992) Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats. J Endocrinol 133:421–431PubMedCrossRefGoogle Scholar
  23. 23.
    Lemmey AB, Martin AA, Read LC, et al. (1991) IGF-I and the truncated analogue des-(1-3)IGF-I enhance growth in rats after gut resection. Am J Physiol 260:E213–E219PubMedGoogle Scholar
  24. 24.
    Heinz-Erian P, Kessler U, Funk B, et al. (1992) Identification and in situ localization of the insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor in the rat gastrointestinal tract: comparison with the IGF-I receptor. Endocrinology 129:1769–1778CrossRefGoogle Scholar

Copyright information

© Springer Science&#x002B;Business Media, Inc. 2006

Authors and Affiliations

  • Shyr-Ming Sheen-Chen
    • 1
    • 2
    • 3
    • 4
  • Hsin-Tsung Ho
    • 3
  • Lu Chia-Pei
    • 1
  • Kuo-Sheng Hung
    • 1
  • Hock-Liew Eng
    • 2
  1. 1.Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung College of MedicineChang Gung UniversityTao-YuanTaiwan
  2. 2.Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung College of MedicineChang Gung UniversityTao-YuanTaiwan
  3. 3.Department of Laboratory Medicine, Mackay Memorial Hospital, Mackay MedicineNursing and Management CollegeTaipeiTaiwan
  4. 4.Department of SurgeryChang Gung Memorial HospitalKaohsiung HsienTaiwan

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