title: Development of a rat model of D-galactosamine/lipopolysaccharide induced hepatorenal syndrome.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Yan
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jing-Yang
authors.initials: JY
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yi-Tong
authors.initials: YT
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Wei-Shu
authors.initials: WS
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Ming-Xiang
authors.initials: MX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005688:Galactosamine; D005919:Glomerular Filtration Rate; D006530:Hepatorenal Syndrome / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009336:Necrosis; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D005688:Galactosamine
keywords: Animal model; D-galactosamine; Hepatorenal syndrome; Lipopolysaccharide; Rat