Hanyang Med Rev.  2013 Aug;33(3):142-149. 10.7599/hmr.2013.33.3.142.

Experiment of Ischemia/Reperfusion Injury of the Cirrhotic Liver in the Murine Mouse Model

Affiliations
  • 1Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, Keimyung University School of Medicine, Daegu, Korea. kjkang@dsmc.or.kr

Abstract

As a medical doctor, the final goal of any type of research is focused on better treatment or contemporary care of the patient. As a surgeon, the research is focused on improving results in surgical procedure and improving the immediate to long term outcomes. In human beings, hepatobiliary tract and pancreas (HBP) play a major role in digestion, body metabolism and endocrine function. These organs are sophisticated in pathology as well as anatomy and physiology. The surgery of the hepatobiliary and pancreatic organ is very difficult. Therefore, the hepatobiliary surgeon's endeavor to treat patients who have hepatobiliary and pancreatic diseases should be scientific and based on evidence in order to get the best result. Here I describe the topic of ischemia/reperfusion injury of the liver from my experience to establish safe surgical resection of the liver with limited bleeding and ischemia/reperfusion injury. Furthermore, I have added ischemia/reperfusion injury in the cirrhotic mouse model, methodology and brief result that I have achieved.

Keyword

Liver; Reperfusion Injury; Animal Experimentation; Liver Cirrhosis; Apoptosis

MeSH Terms

Animal Experimentation
Animals
Apoptosis
Digestion
Hemorrhage
Humans
Liver
Liver Cirrhosis
Mice
Pancreas
Pancreatic Diseases
Reperfusion Injury

Figure

  • Fig. 1 Protocol of hepatic ischemia/reperfusion of the experimental mouse. (A) Intermittent clamping, five cycles of repeated ischemia for 15 minutes and reperfusion for 5 minutes. (B) Ischemic preconditioning, ischemia for 10 minutes and reperfusion for 15 minutes, then prolonged ischemia for 75 minutes. (C) Control, continuous 75 minutes ischemia.

  • Fig. 2 Clamping of the portal triad of the mouse liver.

  • Fig. 3 Intracellular signal pathway of apoptosis.

  • Fig. 4 TUNEL stain. (A) Negative for TUNEL stains, (B) Positive for TUNEL stain, multiple green colored fluorescent stained nuclei are shown, which reflects injured DNA of the hepatocyte nucleus. Ref. 4 with permission from John Wiley and Sons.

  • Fig. 5 DNA laddering. Agarose gel electrophoresis of DNA from livers after reperfusion for 3 hours. (A) Known markers are shown comparing the experimental material. (B) Varying ischemic insults showed no DNA laddering in both intermittent clamping. (C) By contrast, the livers subjected to continuous ischemia showed the typical laddering pattern indicating DNA fragmentation. Ref. 7 with permission from Elsevier.

  • Fig. 6 Trichrome stained experimental mouse liver. (A) After intraperitoneal injection of 50% solution of CCl4 for 10 weeks. (B) After oral ingestion of thioacetamide solution for 10 weeks.

  • Fig. 7 Isolated perfused rat liver model.


Cited by  1 articles

Role of Experimental Research as a Surgeon
Hwon Kyum Park
Hanyang Med Rev. 2013;33(3):139-141.    doi: 10.7599/hmr.2013.33.3.139.


Reference

1. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986; 74:1124–1136.
Article
2. Gao W, Bentley RC, Madden JF, Clavien PA. Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation. Hepatology. 1998; 27:1652–1660.
Article
3. Yadav SS, Sindram D, Perry DK, Clavien PA. Ischemic preconditioning protects the mouse liver by inhibition of apoptosis through a caspase-dependent pathway. Hepatology. 1999; 30:1223–1231.
Article
4. Kang KJ, Jang JH, Lim TJ, Kang Y, Park KK, Lee IS, et al. Optimal cycle of intermittent portal triad clamping during liver resection in the murine liver. Liver Transpl. 2004; 10:794–801.
Article
5. Yadav SS, Gao W, Harland RC, Clavien PA. A new and simple technique of total hepatic ischemia in the mouse. Transplantation. 1998; 65:1433–1436.
Article
6. Rudiger HA, Kang KJ, Sindram D, Riehle HM, Clavien PA. Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver. Ann Surg. 2002; 235:400–407.
Article
7. Jang JH, Kang KJ, Kim YH, Kang YN, Lee IS. Reevaluation of experimental model of hepatic fibrosis induced by hepatotoxic drugs: an easy, applicable, and reproducible model. Transplant Proc. 2008; 40:2700–2703.
Article
8. Jang JH, Kang KJ, Kang Y, Lee IS, Graf R, Clavien PA. Ischemic preconditioning and intermittent clamping confer protection against ischemic injury in the cirrhotic mouse liver. Liver Transpl. 2008; 14:980–988.
Article
9. Sindram D, Porte RJ, Hoffman MR, Bentley RC, Clavien PA. Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver. Gastroenterology. 2000; 118:183–191.
Article
10. Caban A, Oczkowicz G, Abdel-Samad O, Cierpka L. Influence of ischemic preconditioning and nitric oxide on microcirculation and the degree of rat liver injury in the model of ischemia and reperfusion. Transplant Proc. 2006; 38:196–198.
Article
11. Alchera E, Tacchini L, Imarisio C, Dal Ponte C, De Ponti C, Gammella E, et al. Adenosine-dependent activation of hypoxia-inducible factor-1 induces late preconditioning in liver cells. Hepatology. 2008; 48:230–239.
Article
12. Selzner M, Bielawska A, Morse MA, Rudiger HA, Sindram D, Hannun YA, et al. Induction of apoptotic cell death and prevention of tumor growth by ceramide analogues in metastatic human colon cancer. Cancer Res. 2001; 61:1233–1240.
13. Sakamoto Y, Makuuchi M, Takayama T, Minagawa M, Kita Y. Pringle's maneuver lasting 322 min. Hepatogastroenterology. 1999; 46:457–458.
14. Clavien PA, Sanabria JR, Cywes R, Harvey PR, Strasberg SM. A method for sequential excision biopsies of rat liver in an isolated perfused system. Liver. 1992; 12:69–72.
Article
15. Cosimi AB. Surgeons and the Nobel Prize. Arch Surg. 2006; 141:340–348.
Article
16. Yang JD, Seol SY, Leem SH, Kim YH, Sun Z, Lee JS, et al. Genes associated with recurrence of hepatocellular carcinoma: integrated analysis by gene expression and methylation profiling. J Korean Med Sci. 2011; 26:1428–1438.
Article
Full Text Links
  • HMR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr