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Validation of a surgical model for posthepatectomy liver failure in rats

Animal Models and Experimental Medicine 2023年第3期6卷 266-273页

作者： Andrea Lund Michelle Meier Kasper Jarlhelt Andersen Marie Ingemann Pedersen Anders Riegels Knudsen Jakob Kirkegård Frank Viborg Mortensen Aarhus University Hospital Department of Upper Gastrointestinal and Hepato-Pancreato-Biliary SurgeryAarhus NDenmark

Background:The upper limit for liver resections in rats is approximately 90%.In the early postoperative phase,mortality increases.The aim of the present study was to validate the rat model of 90%partial hepatectomy(PH)as a model of post-hepatectomy liver failure(PHLF).Further,we wanted to test a quantitative scoring system as a detector of lethal outcomes caused by PHLF in rats.Methods:Sixty-eight rats were randomized to 90%PH,sham operation,or no sur-gery.Further,block randomization was performed based on time of euthanization:12,24,or 48 h after surgery.A general distress score(GDS)≥10 during the day or≥6 at midnight prompted early euthanization and classification as nonsurvivor.Animals euthanized as planned were classified as survivors.During euthanization,blood and liver tissue were collected,and liver-specific biochemistry was evaluated.Results:Based on the biochemical results,all animals subjected to 90%PH expe-rienced PHLF.Seventeen rats were euthanized due to irreversible PHLF.The GDS increased for nonsurvivors within 12–18 h after surgery.The mean time for euthaniza-tion was 27 h after surgery.Conclusion:Based on the GDS and liver-specific biochemistry,we concluded that the model of 90%PH seems to be a proper model for investigating PHLF in rats.As a high GDS is associated with increased mortality,the GDS appears to be valuable in detect-ing lethal outcomes caused by PHLF in rats.

关键词： 90%liver resection general distress score liver failure post-hepatectomy liver failure rats

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Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis

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World Journal of Hepatology 2018年第1期10卷 8-21页

作者： David Haldrup Sara Heeboll Karen Louise Thomsen Kasper Jarlhelt Andersen Michelle Meier Frank Viborg Mortensen Jens Randel Nyengaard Stephen Hamilton-Dutoit Henning Gronbaek Department of Hepatology and Gastroenterology Aarhus University HospitalAarhus C DK-8000Denmark Department of Internal Medicine Randers Regional HospitalRanders NO DK-8930Denmark Department of Surgical Gastroenterology Aarhus University HospitalAarhus C DK-8000Denmark Stereology and Electron Microscopy Laboratory Centre for Stochastic Geometry and Advanced BioimagingAarhus University HospitalAarhus C DK-8000Denmark Institute of Pathology Aarhus University HospitalAarhus C DK-8000Denmark

AIM To evaluate the liver regeneration capacity(LRC) after partial hepatectomy(PH) in experimental non-alcoholic steatohepatitis(NASH).METHODS Fifty-four female rats were fed a high-fat, high-cholesterol diet(HFCD, 65% fat, 1% cholesterol) or standard diet(STD) for 16 wk. A 70% PH was performed and the animals were euthanised before PH or 2 or 5 d postPH. LRC was evaluated using: The total number of Ki-67 positive hepatocytes in the caudate lobe, N(Ki-67, lobe) evaluated in a stereology-based design, the regenerated protein ratio(RPR), prothrombin-proconvertin ratio(PP), and m RNA expression of genes related to regeneration.RESULTS The HFCD NASH model showed significant steatosis with ballooning and inflammation, while no fibrosis was present. Mortality was similar in HFCD and STD animals following PH. HFCD groups were compared to respective STD groups and HFCD animals had a significantly elevated alanine transaminase at baseline(P < 0.001), as well as a significantly elevated bilirubin at day 2 after PH(P < 0.05). HFCD animals had a higher N(Ki-67, lobe) at baseline,(P < 0.0001), day 2 after PH(P = 0.06) and day 5 after PH(P < 0.025). We found no significant difference in RPR or PP neither 2 or 5 d post-PH. Expression of liver regeneration genes(e.g., hepatic growth factor) was higher at both day 2 and 5 post-PH in HFCD groups(P < 0.05).CONCLUSION NASH rats had a preserved LRC after hepatectomy when compared to STD rats. The methods and models of NASH are essential in understanding and evaluating LRC.

关键词： Rat Non-alcoholic fatty liver Non-alcoholic steatohepatitis Liver regeneration Hepatectomy Ki-67 Gene expression

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