Modified Rat-Tail-Fixed Model of Parenteral Nutrition to Study Liver Injury

  • Linlin Li
  • Mingxiao GuoEmail author
Original Article


For patients with intestinal failure, parenteral nutrition (PN) is a life-saving therapy. Unfortunately, PN does have serious adverse effects. The purpose of our study was to establish a tail-fixed and reproducible animal model of PNALD in which to explore the pathogenesis and evaluate various potential therapeutic manipulations as potential methods of treatment or prevention. Forty SD rats were randomly assigned to parenteral nutrition group or control group. A central venous catheter was inserted for intravenous infusion of a total parenteral nutrition solution (TPN group) or saline (control group) for 1 week or 2 weeks. Survival rate, hepatic biochemical tests, and liver pathology were analyzed. There was no significant difference in survival rate between the two groups at 1 and 2 weeks. The TPN group showed significant increases in direct bilirubin, total bilirubin, and serum aminotransferase than the control group (P < 0.05). Livers in the TPN group had severe, diffuse involvement of hepatocytes by macrovesicular and microvesicular steatosis. The pathological scores were significantly higher in the TPN group than the control group (P < 0.05). The model provides the opportunity to further investigate pathogenesis and treatment of parenteral nutrition–associated liver disease.


Parenteral nutrition–associated liver disease Models Rat Tail-fixed 


Funding Information

This study was supported by the National Natural Science Foundation of China (Grant No. 81500688), Shandong Provincial Natural Science Foundation of China (Grant No. ZR2015HL033), and Shandong Provincial medical and health science and technology development program (Grant No. 2016WS0237).

Compliance with Ethical Standards

All procedures were carried out in accordance with “The Principles of Laboratory Animal Care,” formulated by the National Society of Medical Research, and “The Guide for the Care and Use of Laboratory Animals” published by the US National Institutes of Health (publication No. 85-23, revised 1996). The experimental protocol was approved by the Animal Research Committee of Linyi Hospital.

Conflict of Interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Mitra A, Ahn J (2017) Liver disease in patients on total parenteral nutrition. Clin Liver Dis 21:687–695CrossRefGoogle Scholar
  2. 2.
    Israelite JC (2017) Pediatric parenteral nutrition-associated liver disease. J Infus Nurs 40:51–54Google Scholar
  3. 3.
    Whitehead A, Schwartz MZ (2016) Development of a reproducible model of parenteral nutrition-associated liver disease in rats. Eur J Pediatr Surg 26:96–99Google Scholar
  4. 4.
    Zhu X, Zhang X, Yu L, Xu Y, Feng X, Wang J (2015) Hepatic overexpression of GRP94 in a rabbit model of parenteral nutrition-associated liver disease. Gastroenterol Res Pract 2015:269831CrossRefGoogle Scholar
  5. 5.
    Xu Z, Sun Y (2019) The role of parenteral lipids in the development of hepatic dysfunction and hepatic steatosis in a mouse model of total parenteral nutrition. J Nutr Sci Vitaminol (Tokyo) 65:24–30Google Scholar
  6. 6.
    Li Z, Yang S, Lin H et al (2003) Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 37:343–350CrossRefGoogle Scholar
  7. 7.
    Carter BA, Shulman RJ (2007) Mechanisms of disease: update on the molecular etiology and fundamentals of parenteral nutrition associated cholestasis. Nat Clin Pract Gastroenterol Hepatol 4:277–287CrossRefGoogle Scholar
  8. 8.
    Al-Shahwani NH, Sigalet DL (2017) Pathophysiology, prevention, treatment, and outcomes of intestinal failure-associated liver disease. Pediatr Surg Int 33:405–411CrossRefGoogle Scholar
  9. 9.
    Cahova M, Bratova M, Wohl P (2017) Parenteral nutrition-associated liver disease: the role of the gut microbiota. Nutrients 9:E987CrossRefGoogle Scholar
  10. 10.
    Alemmari A, Miller GG, Arnold CJ, Zello GA (2011) Parenteral aluminum induces liver injury in a newborn piglet model. J Pediatr Surg 46:883–887CrossRefGoogle Scholar
  11. 11.
    Muto M, Lim D, Soukvilay A, Field C, Wizzard PR, Goruk S, Ball RO, Pencharz PB, Mi S, Curtis J, Wales PW, Turner JM (2017) Supplemental parenteral vitamin E into conventional soybean lipid emulsion does not prevent parenteral nutrition-associated liver disease in full-term neonatal piglets. J Parenter Enter Nutr 41:575–582CrossRefGoogle Scholar
  12. 12.
    Vilahur G, Padro T, Badimon L (2011) Atherosclerosis and thrombosis: insights from large animal models. J Biomed Biotechnol 2011:907575CrossRefGoogle Scholar

Copyright information

© Association of Surgeons of India 2019

Authors and Affiliations

  1. 1.Department of Surgery, Linyi Municipal Mental Health CenterLinyi Fourth People’s HospitalLinyiChina
  2. 2.Department of General Surgery, Linyi People’s HospitalShandong UniversityLinyiChina

Personalised recommendations