Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2015; 21(34): 9927-9935
Published online Sep 14, 2015. doi: 10.3748/wjg.v21.i34.9927
Development of a rat model of D-galactosamine/lipopolysaccharide induced hepatorenal syndrome
Jing-Bo Wang, Hai-Tao Wang, Lu-Ping Li, Ying-Chun Yan, Wei Wang, Jing-Yang Liu, Yi-Tong Zhao, Wei-Shu Gao, Ming-Xiang Zhang
Jing-Bo Wang, Lu-Ping Li, Ying-Chun Yan, Wei Wang, Jing-Yang Liu, Yi-Tong Zhao, Wei-Shu Gao, Ming-Xiang Zhang, Cirrhosis Treatment Center, the Sixth People′s Hospital of Shenyang, Shenyang 110006, Liaoning Province, China
Hai-Tao Wang, Department of General Surgery, the Affiliated Shenzhou Hospital of Shenyang Medical College, Shenyang 110001, Liaoning Province, China
Author contributions: Wang JB, Wang HT and Zhang MX contributed equally to this work, and all of them were involved in the design and performing of the experiment, data analysis and drafting of the article; Li LP, Yan YC and Gao WS participated in the design and performing of the study and biochemical test; Wang W, Liu JY and Zhao YT the completed hepatic and renal pathological examination, data analysis and drafting of the paper.
Institutional animal care and use committee statement: This study was approved by the Ethical Committee of Shenyang Sixth People’s Hospital.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ming-Xiang Zhang, Professor, Cirrhosis Treatment Center, the Sixth People′s Hospital of Shenyang, 85 Hepingnan Street, Heping District, Shenyang 110006, Liaoning Province, China. zhangmingxiang2014@126.com
Telephone: +86-24-23387410-116
Received: March 15, 2015
Peer-review started: March 15, 2015
First decision: April 13, 2015
Revised: June 3, 2015
Accepted: June 26, 2015
Article in press: June 26, 2015
Published online: September 14, 2015
Processing time: 183 Days and 7 Hours
Abstract

AIM: To develop a practical and reproducible rat model of hepatorenal syndrome for further study of the pathophysiology of human hepatorenal syndrome.

METHODS: Sprague-Dawley rats were intravenously injected with D-galactosamine and lipopolysaccharide (LPS) via the tail vein to induce fulminant hepatic failure to develop a model of hepatorenal syndrome. Liver and kidney function tests and plasma cytokine levels were measured after D-galactosamine/LPS administration, and hepatic and renal pathology was studied. Glomerular filtration rate was detected in conscious rats using micro-osmotic pump technology with fluorescein isothiocyanate-labelled inulin as a surrogate marker.

RESULTS: Serum levels of biochemical indicators including liver and kidney function indexes and cytokines all significantly changed, especially at 12 h after D-galactosamine/LPS administration [alanine aminotransferase, 3389.5 ± 499.5 IU/L; blood urea nitrogen, 13.9 ± 1.3 mmol/L; Cr, 78.1 ± 2.9 μmol/L; K+, 6.1 ± 0.5 mmol/L; Na+, 130.9 ± 1.9 mmol/L; Cl-, 90.2 ± 1.9 mmol/L; tumor necrosis factor-α, 1699.6 ± 599.1 pg/mL; endothelin-1, 95.9 ± 25.9 pg/mL; P < 0.05 compared with normal saline control group]. Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/LPS, and was characterized by massive hepatocyte necrosis, while the structures of glomeruli, proximal and distal tubules were normal. Glomerular filtration rate was significantly decreased to 30%-35% of the control group at 12 h after D-galactosamine/LPS administration [Glomerular filtration rate (GFR)1, 0.79 ± 0.11 mL/min; GFR2, 3.58 ± 0.49 mL/min·kgBW-1; GFR3, 0.39 ± 0.99 mL/min·gKW-1]. The decreasing timing of GFR was consistent with that of the presence of hepatocyte necrosis and liver and kidney dysfunction.

CONCLUSION: The joint use of D-galactosamine and LPS can induce liver and kidney dysfunction and decline of glomerular filtration rate in rats which is a successful rat model of hepatorenal syndrome.

Keywords: Hepatorenal syndrome; Animal model; Rat; D-galactosamine; Lipopolysaccharide

Core tip: In this article, D-galactosamine was injected into SD rats via the caudal vein to establish a model of hepatorenal syndrome (HRS). Twelve hours after injection, serum level of tumor necrosis factor-alpha was significantly elevated while the glomerular filtration rate was significantly lowered. Hepatorenal function became obviously abnormal. Pathological findings showed massive necrosis of liver cells but normal kidney structure. Our animal model provided a good simulation of partial pathophysiological process of human HRS.