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/m L; endothelin-1,95.9 ± 25.9 pg/m L; 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 m L/min; GFR2,3.58 ± 0.49 m L/min·kg BW-1; GFR3,0.39 ± 0.99 m L/min·g KW-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. 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-labeled 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 / m L; endothelin-1,95.9 ± 25.9 pg / 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 The 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 m L / min; GFR2, 3.58 ± 0.49 m L / min · kg BW-1; GFR3,0.39 ± 0.99 m L / min · g KW-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 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 o f hepatorenal ssyndrome.