Skip to main content

Advertisement

SpringerLink
Log in

Partial Portal Vein Ligation Plus Thioacetamide: A Method to Obtain a New Model of Cirrhosis and Chronic Portal Hypertension in the Rat

  • Published:
Journal of Gastrointestinal Surgery

Abstract

To obtain a new model of chronic portal hypertension in the rat, two classical methods to produce portal hypertension, partial portal vein ligation and the oral administration of thioacetamide (TAA), have been combined. Male Wistar rats were divided into four groups: 1 (control; n = 10), 2 [triple partial portal vein ligation (TPVL); n = 9], 3 (TAA; n = 11), and 4 (TPVL plus TAA; n = 9). After 3 months, portal pressure, types of portosystemic collateral circulation, laboratory hepatic function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase) and liver histology were studied. The animals belonging to group 2 (TPVL) developed extrahepatic portosystemic collateral circulation, associated with mesenteric venous vasculopathy without hepatic destructurization or portal hypertension. Animals from group 3 (TAA) developed cirrhosis and portal hypertension but not extrahepatic portosystemic collateral circulation, or mesenteric venous vasculopathy. Finally, the animals from group 4 (TPVL + TAA) developed cirrhosis, portal hypertension, portosystemic collateral circulation, and mesenteric venous vasculopathy. The association of TPVL and TAA can be used to obtain a model of chronic portal hypertension in the rat that includes all the alterations that patients with hepatic cirrhosis usually have. This could, therefore, prove to be a useful tool to study the pathophysiological mechanisms involved in these alterations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Muller A, Machnik F, Zimmermann T, Schubert H. Thioacetamide-induced cirrhosis-like lesions in rats—usefulness and reliability of this animal model. Exp Pathol 1998;34:229–236.

    Google Scholar 

  2. Li X, Benjamin IS, Alexander B. Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality. J Hepatol 2002;36:488–493.

    Article  PubMed  Google Scholar 

  3. Mas MR, Comer B, Oncu K, Vural SA, Akay C, Tasci I, Ozkomur E, Serdar M, Mas N, Alcigir G, Yener N. The effect of taurine treatment on oxidative stress in experimental liver fibrosis. Hepatol Res 2004;28:207–215.

    Article  PubMed  CAS  Google Scholar 

  4. Benoit JN, Barrowman JA, Harper SL, Kvietys PR, Granger DN. Role of humoral factors in the intestinal hyperemia associated with chronic portal hypertension. Am J Physiol (Gastrointest Liver Physiol 10) 1984;247:G486–G493.

    CAS  Google Scholar 

  5. Lopez-Talavera JC, Merrill WW, Groszmann RJ. Tumor necrosis factor α: A major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats. Gastroenterology 1995;108:761–767.

    Article  PubMed  CAS  Google Scholar 

  6. Orloff MJ. Portal hypertension and portocaval shunt. In WW Souba, DW Wilmore Eds., Surgical research vol. 49 London: Academic, 2001, pp. 637–701.

    Google Scholar 

  7. Lopez-Talavera JC, Cadelina G, Merrill WW, Groszmann RJ. Role of tumor necrosis factor-alpha in the circulatory abnormalities of cirrhotic rats. Hepatology 1995;22:256A.

    Google Scholar 

  8. Sikuler E, Kravetz D, Groszmann RJ. Evolution of portal hypertension and mechanisms involved in its maintenance in a rat model. Am J Physiol (Gastrointest Liver Physiol 11) 1985;248:G618–G625.

    CAS  Google Scholar 

  9. McMathuna P, Vlavianos P, Westaby D, Williams R. Pathophysiology of portal hypertension. Dig Dis 1992;10(suppl 1):3–15.

    Article  Google Scholar 

  10. Chojkier M, Groszmann RJ. Measurement of portal-systemic shunting in the rat by using γ-labeled microspheres. Am J Physiol (Gastrointest Liver Physiol 3) 1981;240:G371–G375.

    CAS  Google Scholar 

  11. Hori N, Okanoue T, Sawa Y, Mori T, Kashima K. Hemodynamic characterization in experimental liver cirrhosis induced by thioacetamide administration. Dig Dis Sci 1993;38:2195–2202.

    Article  PubMed  CAS  Google Scholar 

  12. Sherlock S. The portal venous system and portal hypertension. In S. Sherlock Ed., Diseases of the liver and biliary system 8th ed. London: Blackwell, 1989 pp. 151–207).

    Google Scholar 

  13. Monterde G, Rodriguez-Fabian G, Vara E, Lopez L, Arias J, Aller MA, Arias J. Increased plasma levels of corticosterone and prolactin and decreased T3 and T4 levels in short-term prehepatic portal hypertension in rats. Dig Dis Sci 2000;45:1865–1871.

    Article  PubMed  CAS  Google Scholar 

  14. Dieguez B, Aller MA, Nava MP, Arias JL, Lopez L, Arias J. Chronic portal hypertension in the rat by triple-portal stenosing ligation. J Inves Surg 2002;15:329–336.

    Article  CAS  Google Scholar 

  15. Castañeda B, Dubernardi-Venon W, Bandi JC, Andreu V, Perez del Pulgar S, Moitinho E, Pizcueta P, Bosch J The role of portal pressure in the severity of bleeding in portal hypertensive rats. Hepatology 2000;31:581–586.

    Article  PubMed  Google Scholar 

  16. Kravetz D, Sikuler E, Groszmann RJ. Splanchnic and systemic hemodynamics in portal hypertensive rats during hemorrhage and blood volume restitution. Gastroenterology 1986;90:1232–1240.

    PubMed  CAS  Google Scholar 

  17. Knodell RG, Ishak KG, Black WC, Chen TS, Graig R, Kaplowitz N, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431–435.

    Article  PubMed  CAS  Google Scholar 

  18. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Schever PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1519.

    Article  PubMed  CAS  Google Scholar 

  19. Nakata M, Nakamura K, Koda Y, Kaminou T, Ugami M, Kaneda K, Yamada R. Hemodynamics in the microvasculature of thioacetamide-induced cirrhotic rat livers. Hepato-Gastroenterol 2002;49:652–656.

    PubMed  Google Scholar 

  20. Garcia-Tsao G, Wiest R. Gut microflora in the pathogenesis of the complications of cirrhosis. Best Pract Res Clin Gastroenterol 2004 2004;18:353–372.

    Article  Google Scholar 

  21. Fernandez M, Vizzutti F, Garcia-Pagan JC, Rodes J, Bosch J. Anti-VEGF receptor-2 monoclonal antibody prevent portal-systemic collateral vessel formation in portal hypertensive mice. Gastroenterology 2004;126:886–894.

    Article  PubMed  CAS  Google Scholar 

  22. Moreau R. VEGF-induced angiogenesis drives collateral circulation in portal hypertension. J Hepatol 2005;43:6–8.

    Article  PubMed  CAS  Google Scholar 

  23. Diez-Arias JA, Aller MA, Palma MD, Arias JL, Muñiz E, Sanchez M, Arias J. Increased duodenal mucosa infiltration by mast cells in rats with portal hypertension. Dig Surg 2001;18:34–40.

    Article  PubMed  CAS  Google Scholar 

  24. Prieto I, Aller MA, Santamaria L, Nava MP, Madero R, Perez-Robledo JP, Arias J. Prehepatic portal hypertension produces increased mast cell density in the small bowel and in mesenteric lymph node in the rat. J Gastroenterol Hepatol 2005;20:1025–1031.

    Article  PubMed  Google Scholar 

  25. Lopez L, Gonzalez-Pardo H, Aller MA, Nava MP, Duran HJ, Arias J, Arias JL. Actividad de citocromo oxidasa esplacnica en ratas con hipertensión portal. Rev Esp Enf Dig Madrid 2001;93:794–799.

    CAS  Google Scholar 

  26. Wang JJ, Gao G-W, Gao R-Z, Liu Ch-A, Ding X, Yao Z-X. Effects of tumor necrosis factor, endothelin and nitric oxide on hyperdynamic circulation of rats with acute and chronic portal hypertension. World J Gastroenterol 2004;10:689–693.

    PubMed  CAS  Google Scholar 

  27. Dashti H, Jeppsson B, Hägerstrand I, Hultberg B, Srinivas U, Abdulla M, Bengmark S. Thioacetamide-and carbon tetrachloride-induced liver cirrhosis. Eur Surg Res 1989;21:83–91.

    PubMed  CAS  Google Scholar 

  28. Chen S, Wang H-T, Yang B, Ou, Q-J. Protective effects of recombinant human growth hormone on cirrhotic rats. World J Gastroenterol 2004;10:2894–2897.

    PubMed  CAS  Google Scholar 

  29. Medina J, Arroyo AG, Sanchez-Madrid F, Moreno-Otero R. Angiogenesis in chronic inflammatory liver disease. Hepatology 2004;39:1185–1195.

    Article  PubMed  CAS  Google Scholar 

  30. Suneyama TK, Ohba K, Zen Y, Sato Y, Niwa H, Minato H, Nakanuma Y. A comparative histological and morphometric study of vascular changes in idiopathic portal hypertension and alcoholic fibrosis/cirrhosis. Histopathology 2003;43:55–61.

    Article  Google Scholar 

  31. Ward NL, Haninec AL, Van Slyke P, Sled JG, Sturk C, Henkelman RM, Wanless IR, Dumont DJ. Angiopoietin-1 causes reversible degradation of the portal microcirculation in mice: Implications for treatment of liver disease. Am J Pathol 165:889–899.

    PubMed  CAS  Google Scholar 

  32. Kishore R, Quin G, Luedemann C, Bord E, Hanley A, Silver M, Goukassian D, Losordo DW. The cytoskeletal protein ezrin regulates EC proliferation and angiogenesis via TNF-alpha-induced transcriptional repression of cyclin A. J Clin Invest 2005;115:1785–1796.

    Article  PubMed  CAS  Google Scholar 

  33. Ridnour LA, Isenberg JS, Espey MG, Thomas DD, Roberts DD, Wink DA. Nitric oxide regulates angiogenesis through a functional switch involving thrombospondin-1. Proc Natl Acad Sci USA 2005;102:13147–13152.

    Article  PubMed  CAS  Google Scholar 

  34. Prieto I, Jimenez F, Aller MA, Nava MP, Vara E, Garcia C, Arias J. Tumor necrosis factor-alpha, interleukin-1 beta and nitric oxide: induction of liver megamitochondria in prehepatic portal hypertensive rats. World J Surg 2005;29:903–908.

    Article  PubMed  Google Scholar 

  35. Aller MA, Vara E, Garcia C, Palma MD, Arias JL, Nava MP, Arias J. Proinflammatory liver and antiinflammatory intestinal mediators involved in portal hypertensive rats. Mediators Inflamm 2005;2:101–111.

    Article  CAS  Google Scholar 

  36. Palma MD, Aller MA, Vara E, Nava MP, Garcia C, Arias-Diaz J, Balibrea JL, Arias J. Portal hypertension produces an evolutive hepato-intestinal pro- and anti-inflammatory response in the rat. Cytokine 2005;31:213–226.

    Article  PubMed  CAS  Google Scholar 

  37. Corcuera MT, Nava MP, Angulo A, Aller MA, Gomez F, Casado I, Alonso MJ, Arias J. Splanchnic remodeling secondary to experimental prehepatic portal hypertension. An Med Inter 2005;22:317–322.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Psychobiology Department, Psychology School, University of Oviedo, Asturias, Spain

    Marta Méndez-López, Magdalena Méndez, Laudino López & Jorge-Luis Arias

  2. Surgery Chair, Surgery Department I, Medical School, Complutense University, Madrid, Spain

    Fernando Sánchez-Patán, Maria-Angeles Aller & Jaime Arias

  3. Pathology Service, Hospital Carlos III, Madrid, Spain

    Isabel Casado, Maria-Teresa Corcuera & Maria-Jose Alonso

  4. Animal Physiology Department (Physiology II), School of Biological Sciences, Complutense University of Madrid, Madrid, Spain

    Maria-Paz Nava

  5. Cátedra de Cirugía, Facultad de Medicina, Universidad Complutense de Madrid, Pza. de Ramón y Cajal s.n., 28040, Madrid, Spain

    Maria-Angeles Aller

Authors
  1. Marta Méndez-López
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Magdalena Méndez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fernando Sánchez-Patán
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Isabel Casado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria-Angeles Aller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laudino López
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maria-Teresa Corcuera
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maria-Jose Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maria-Paz Nava
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jaime Arias
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jorge-Luis Arias
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria-Angeles Aller.

Additional information

This work has been supported by a grant from Fundacion Mutua Madrileña Automovilista (ref. number: SV-04-FMM-02)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Méndez-López, M., Méndez, M., Sánchez-Patán, F. et al. Partial Portal Vein Ligation Plus Thioacetamide: A Method to Obtain a New Model of Cirrhosis and Chronic Portal Hypertension in the Rat. J Gastrointest Surg 11, 187–194 (2007). https://doi.org/10.1007/s11605-006-0063-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-006-0063-1

Keywords

Search

Navigation