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

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 

作者机构：Department of Hepatology and GastroenterologyAarhus University HospitalAarhus C DK-8000Denmark Department of Internal MedicineRanders Regional HospitalRanders NO DK-8930Denmark Department of Surgical GastroenterologyAarhus University HospitalAarhus C DK-8000Denmark Stereology and Electron Microscopy LaboratoryCentre for Stochastic Geometry and Advanced BioimagingAarhus University HospitalAarhus C DK-8000Denmark Institute of PathologyAarhus University HospitalAarhus C DK-8000Denmark 

出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)

年 卷 期：2018年第10卷第1期

页      面：8-21页

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：Supported by NOVO Nordisk Foundation(grant number 1013267) Savværksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat to Gr?nb?k H Villum Fonden to Nyengaard JR 

主　　题：Rat Non-alcoholic fatty liver Non-alcoholic steatohepatitis Liver regeneration Hepatectomy Ki-67 Gene expression 

摘      要：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.