Zhang B H, Weltman M, Farrell G C
Department of Medicine, University of Sydney at Westmead Hospital, NSW, Australia.
J Gastroenterol Hepatol. 1999 Feb;14(2):133-7. doi: 10.1046/j.1440-1746.1999.01822.x.
Impaired liver regeneration is a feature of alcoholic hepatitis, but the relative importance of alcohol, nutritional imbalance and inflammatory mediators in causing this effect is unclear. Non-alcoholic steatohepatitis (NASH) is a form of liver disease with similar morphology to alcoholic hepatitis, but the effect of this disorder on liver regeneration is unclear. We, therefore, examined the status of liver regeneration in a rat nutritional model of hepatic steatosis with inflammation, which is morphologically identical to NASH in humans.
Male Wistar rats received a methionine-choline-deficient diet (MCDD) for 4 weeks before experiments and both isocaloric pair-fed and ad libitum-fed rats were used as controls. Following partial hepatectomy (68%), the extent of hepatic regeneration was determined 24 h later using [3H]-thymidine incorporation and restitution of liver mass.
There was no significant difference of [3H]-thymidine incorporation in MCDD-fed, pair-fed and ad libitum-fed rats (80+/-27, 78+/-11 and 80+/-6.3 d.p.m./microg DNA, respectively). Similarly, restituted liver masses in three groups of rats were not significantly different (17+/-3.8, 18+/-1.8 and 17+/-3.1% initial liver weight, respectively).
The similarities in hepatic histology and cytochrome P450 2E1 induction between this nutritional model of hepatic steatohepatitis and alcoholic steatohepatitis imply that these two disorders share pathogenetic mechanisms. However, liver regeneration is not altered by NASH in rats, indicating that the nutritional and inflammatory changes that appear similar to those of alcoholic liver disease do not cause impairment of liver regeneration.
肝再生受损是酒精性肝炎的一个特征，但酒精、营养失衡和炎症介质在导致这种效应中的相对重要性尚不清楚。非酒精性脂肪性肝炎（NASH）是一种形态与酒精性肝炎相似的肝脏疾病，但这种疾病对肝再生的影响尚不清楚。因此，我们在一种与人类NASH形态相同的伴有炎症的肝脂肪变性大鼠营养模型中研究了肝再生的状况。
雄性Wistar大鼠在实验前接受蛋氨酸-胆碱缺乏饮食（MCDD）4周，等热量配对喂养和自由进食的大鼠作为对照。在部分肝切除（68%）后，24小时后使用[3H]-胸腺嘧啶核苷掺入法和肝脏重量恢复来确定肝再生的程度。
MCDD喂养组、配对喂养组和自由进食组大鼠的[3H]-胸腺嘧啶核苷掺入量无显著差异（分别为80±27、78±11和80±6.3 d.p.m./μg DNA）。同样，三组大鼠的肝脏重量恢复也无显著差异（分别为初始肝脏重量的17±3.8%、18±1.8%和17±3.1%）。
这种肝脂肪性肝炎营养模型与酒精性脂肪性肝炎在肝脏组织学和细胞色素P450 2E1诱导方面的相似性意味着这两种疾病具有共同的发病机制。然而，NASH不会改变大鼠的肝再生，这表明与酒精性肝病看似相似的营养和炎症变化不会导致肝再生受损。
