Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis
Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis
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DOI：
10.4254/wjh.v10.i1.8
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发表时间：
2018-01-27
影响因子：
2.4
通讯作者：
Gronbaek, Henning
中科院分区：
文献类型：
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作者：
Haldrup, David;Heeboll, Sara;Gronbaek, Henning
目的评价实验性非酒精性脂肪性肝炎（NASH）患者肝部分切除术（PH）后肝脏再生能力（LRC）。方法54只雌性大鼠分别饲喂高脂、高胆固醇饲料（HFCD， 65%脂肪，1%胆固醇）和标准饲料（STD） 16周。PH值为70%，动物在PH前或PH后2或5 d被安乐死。LRC的评估方法包括：尾状叶中Ki-67阳性肝细胞的总数、基于体视学设计的N（Ki-67，叶）、再生蛋白比率（RPR）、凝血酶原-转换蛋白原比率（PP）和再生相关基因的mRNA表达。结果HFCD NASH模型表现为明显的脂肪变性、水肿和炎症，未见纤维化。PH后，HFCD和STD动物的死亡率相似。与各自的STD组比较，HFCD动物在基线时丙氨酸转氨酶显著升高（P < 0.001）， PH后第2天胆红素显著升高（P < 0.05）。HFCD动物在基线（P < 0.0001）、PH后第2天（P = 0.06）和PH后第5天（P < 0.025）均有较高的N（Ki-67, lobe）。我们发现ph后2或5 d的RPR或PP均无显著差异。肝再生基因（如肝生长因子）在ph后第2天和第5天的表达量均高于HFCD组（P < 0.05）。结论与性病大鼠相比，nash大鼠肝切除术后LRC保存完好。NASH的方法和模型对于理解和评估LRC至关重要。
AIMTo evaluate the liver regeneration capacity (LRC) after partial hepatectomy (PH) in experimental non-alcoholic steatohepatitis (NASH).METHODSFifty-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 mRNA expression of genes related to regeneration.RESULTSThe 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).CONCLUSIONNASH 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.