己酮可可碱对高脂饮食大鼠脂肪性肝炎并肝纤维化的干预作用

体内外实验显示，肿瘤坏死因子(TNF-α)抑制剂——己酮可可碱(PTX)有抗肝纤维化作用，然而其对非酒精性脂肪性肝炎(NASH)肝纤维化的影响少见报道。为此，本研究通过高脂饮食复制NASH并肝纤维化模型，探讨PTX对脂肪性肝炎肝纤维化形成的影响。     

己酮可可碱对大鼠非酒精性脂肪性肝炎细胞外基质合成与降解的影响

目的 观察己酮可可碱(PTX)对大鼠非酒精性脂肪性肝炎(NASH)细胞外基质合成与降解的影响.方法 30只SD大鼠随机分为模型组(10只)、治疗组(10只)和正常对照组(10只).模型组大鼠以高脂饲料喂养16周;治疗组大鼠高脂饮食喂养12周后加用己酮可可碱16 mg·kg-1.d-1治疗4周;对照组大鼠以普通饲料喂养16周.在实验16周结束后处死3组所有大鼠,用RT-PCR方法分别测定肝组织细胞外基质合成与降解的指标:Ⅰ、Ⅲ型胶原、TIMP-1、MMP-13的mRNA水平.结果 大鼠肝组织中Ⅰ型胶原mRNA的表达水平,对照组、模型组和治疗组分别为1.466±0.212、1.890±0.078和1.553±0.129,模型组高于对照组(P＜0.05),治疗组显著低于模型组.大鼠肝组织中Ⅲ型胶原mRNA的表达水平,对照组、模型组和治疗组分别为1.803±0.186、2.593±0.306和1.897±0.119,模型组高于对照组(P＜0.05),治疗组显著低于模型组.大鼠肝组织中TIMP-1 mRNA的表达水平,对照组、模型组和治疗组分别为1.313 ±0.031、1.760±0.225和1.780±0.245,模型组及治疗组均高于正常对照组(P＜0.05),治疗组与模型组之间没有明显差异.大鼠肝组织中MMP-13 mRNA的表达水平,对照组、模型组和治疗组分别为0.690±0.026、0.700±0.010和0.821±0.020,模型组与正常对照组无明显差异;治疗组水平较对照组及模型组显著升高(P＜0.05).结论已酮可可碱可降低NASH大鼠肝脏中细胞外基质Ⅰ、Ⅲ型胶原的合成,对TIMP-1的水平无明显影响,但可明显升高肝脏中MMP-13的水平,对NASH引起的肝纤维化有一定的治疗作用.     

己酮可可碱抑制非酒精性脂肪性肝炎TNF-α的实验研究

目的 探讨己酮可可碱pentoxifylline PTX对大鼠非酒精性脂肪性肝炎TNF-α表达的影响.方法 雄性SD大鼠40只,随机分成正常对照组、模型组、治疗组3组,实验需16周.正常对照组(10只)饲以普通饲料,模型组(20只)及治疗组(10只)饲以高脂饲料.12周时从模型组中随机抽取10只处死,病理证实为脂肪性肝炎;余下的模型组及治疗组大鼠继续高脂饲料饲养,同时治疗组大鼠予以PTX16 mg/kg·d灌胃4周.至16周时处死所有剩余大鼠,分别检测各组动物的体重、肝指数、血生化指标;进行HE染色观察肝脏病理学改变;并应用免疫组织化学方法分析和观察TNF-α表达.结果 与模型组比较PTX治疗组大鼠体重、肝指数[(608.50±52.92)g对(668.00±62.86)g,(4.11±0.47)对(4.85±0.61),P＜0.05和P＜0.01]显著降低;肝脏生化得到改善[AST(120.20±34.59)U/L对(221.80±100.36)U/L,P＜0.01];空腹血糖降低[(9.04±0.997)mmol/L对(10.58±1.871)mmol/L,P＜0.05],且肝组织炎症活动度计分明显下降[(5.70±0.94)对(6.72±0.84),P＜0.01].组织化学显示TNF-α在肝脏中的表达显著降低[(0.172±0.042)对(0.43±0.038),P＜0.01].结论 己酮可可碱可改善高脂饮食诱发的脂肪性肝炎大鼠肝脏酶学,减轻肝组织炎症损伤,具有治疗作用;其治疗机制之一可能是抑制TNF-α在肝脏中的表达.     

发现一种与非酒精性脂肪肝相关的基因途径

背景：根据老鼠的脂肪肝模型（MAT1A-KO），我们总结出了与非酒精性脂肪性肝炎（NASH）患者的肝组织病理检查相对应的基因表达方式，以阐明与NASH相关的基因途径。     

茴三硫防治非酒精性脂肪性肝炎的实验研究

目的 非酒精性脂肪性肝炎（NASH）可发展为纤维化、肝硬化、目前尚缺乏有效防治药物。研究茴三硫对大鼠NASH模型形成的影响，为临床防治NASH提供新方法。方法 60只SD大鼠随机平均分为6组，每组10只：正常组喂普通饲料；模型组高脂饲料；茴三硫预防组喂高脂饲料同时，加用茴三硫。余30只大鼠在高脂饮食12周后复分为：茴三硫治疗组，喂高脂饲料同时加用茴三硫；饮食治疗组即恢复正常饲料喂养；茴三硫＋饮食治疗组，恢复正常饮食同时予茴三硫治疗。16周后处死动物。称动物体重、肝脏湿重、检测血清转氨酶，光镜下评估肝脂肪变性和炎症活动程度。结果 茴三硫治疗、饮食治疗、茴三硫＋饮食治疗能显著降低造模大鼠的体重（P＜0．05）、肝指数（P＜0．05）、转氨酶（P＜0．01），还能改善肝脏指肪变性和炎症坏死的程度（P分别＜0．05和＜0．01）。茴三硫预防组的上述各项指标则与无显著差异。结论 茴三硫、饮食治疗NASH有效，两种方法联用可增强疗效。预防性应用茴三硫并无必要。     

枯否氏细胞在大鼠非酒精性脂肪性肝炎发病中的作用

目的：探讨枯否氏细胞大鼠非酒精性脂肪性肝炎（non-alcoholic steatohepatitis,NASH)发病中的作用,方法：19只雄性SD大鼠随机分为模型组（10只）和正常组（9只）,分别预高脂肪饮食和标准饮食饲养12周,HE梁色观察肝细胞切片病理学改变,透射电镜和溶菌酶免疫组织化学染色观察枯否氏细胞的数量和形态。结果：模型组大鼠均出现肥胖,高脂血症伴肝细胞大泡性脂肪变,小叶内炎症细胞浸润和坏死,与正常相比,模型组肝小叶内枯否氏细胞数显著增加,并呈活化状态,模型组枯否氏细胞变化与其肝病理学改变相一致,结论：高脂饮食大鼠肝脏枯否氏细胞增多,并可能与其脂肪性肝炎的发病有关。     

网络抗氧化剂对非酒精性脂肪性肝炎大鼠氧化应激作用的影响

目的探讨网络抗氧化剂对非酒精性脂肪性肝炎（NASH）大鼠氧化应激作用的影响。方法雄性SD大鼠30只,随机分为3组,正常对照组、模型组、网络抗氧化剂组。正常对照组普通饲料喂养,模型组喂高脂饮食,网络抗氧化剂组在高脂饮食12周后给予维生素E（100mg／kg）、维生素C（100mg／kg）、硫辛酸（40mg／kg）、辅酶Q10（100mg／kg）、还原性谷胱甘肽（100mg／kg）混合灌胃治疗。16周末处死各组大鼠,测定血清转氨酶（ALT、AST）及硒-谷胱甘肽过氧化物酶（Se-GSH-PX）活性,光镜下观察肝脏组织病理形态学改变,测定肝组织丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性。结果与正常对照组比较,模型组大鼠血清ALT、AST显著升高（P〈0．05）;肝组织MDA含量增高（P〈0．05）,SOD及Se-GSH-PX活性下降（P〈0．05）;肝脏脂肪变性程度和炎症活动度均有显著增高（P〈0．05）,与模型组比较,网络抗氧化剂组可促进上述指标恢复（P〈0．05）。结论网络抗氧化剂对高脂饮食诱导的大鼠NASH有一定治疗效果,网络抗氧化剂之间协同增强的抗氧化能力有效阻遏了自由基引发的氧化应激,保持了氧化／抗氧化平衡,改善NASH大鼠脂肪变性,减轻炎症反应。     

节制饮食对大鼠非酒精性脂肪性肝炎的治疗作用

非酒精性脂肪性肝病 (nonalcoholicfattyliverdiseases ,NAFLD)可发展为肝纤维化和肝硬化 ,且经过非酒精性脂肪性肝炎 (nonalcoholicsteatohepatitis ,NASH )这一病理阶段[1 3 ] ,因而早期干预是必要的。然而至今尚无治疗NAFLD的特效药物 ,因此作为基本治疗的饮食疗法在NAFLD治疗中的作用越发受到重视。本研究将观察节制饮食对NASH的治疗作用。材料与方法一、材料雄性SD大鼠 2 0只 ,购自西普尔 必凯公司 ,体重 14 0～160 g ,正常喂养 1周后 ,通过高脂饮食 12周建立NASH大鼠模型 ,随机分为 2组 :模型组 10只继予高脂饮食喂养 ;…     

ω-3多不饱和脂肪酸防治非酒精性脂肪性肝炎大鼠的初步观察

目的观察多不饱和脂肪酸对非酒精性脂肪性肝炎（NASH）大鼠糖脂代谢、肝脏脂质沉积及血清脂肪细胞因子的影响。方法随机将32只大鼠分成3组,正常组给予普通饲料喂养,模型组和治疗组给予高脂饲料喂养制备NASH模型。治疗组在喂养8周后加用ω-3多不饱和脂肪酸干预,12周后处死大鼠。比较各组大鼠体重、肝重,空腹血糖、转氨酶、甘油三酯（TG）、总胆固醇（TC）、脂肪细胞因子,以及肝组织学改变。结果 12周后模型组大鼠肝组织病理学检查显示明显脂肪变,动物体重、肝重和各项生化指标均显著高于正常组;与模型组比,治疗组动物体重和生化指标均有改善,其中AST和TC下降有统计学意义（P〈0.05）;治疗组动物血清瘦素、抵抗素呈下降趋势,而脂联素呈升高倾向。结论多不饱和脂肪酸具有改善NASH大鼠糖脂代谢及脂肪细胞因子表达的能力。     

壳脂胶囊对非酒精性脂肪性肝炎大鼠肝组织PPAR-γ、IR的作用研究

[目的]探讨壳脂胶囊对非酒精性脂肪性肝炎大鼠肝组织PPAR-γ、IR的影响.[方法]高脂饮食饲喂SD大鼠以制备非酒精性脂肪性肝炎模型,造模同时进行药物干预.干预8周后,自动生化分析仪检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆固醇（CHO）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、甘油三酯（TG）水平,苏木精-伊红染色、油红O染色观察肝组织病理,RT-PCR检测PPAR-γmRNA和IR mRNA,Western-blot检测PPAR-γ和IR蛋白表达.[结果]与模型组比较,壳脂胶囊能明显降低血清TG、CHO、LDL、AST、ALT水平（P＜0.01）;壳脂胶囊组脂肪变性和炎症反应程度均较模型组有一定的减轻;壳脂胶囊组大鼠PPAR-γ和IR的蛋白和基因表达水平均高于模型组（P＜0.05）.[结论]壳脂胶囊可能通过上调肝组织PPAR-γ、IR蛋白及PPAR-γ mR-NA、IR mRNA的表达,改善胰岛素抵抗,进而调解脂肪代谢,改善肝脏功能,达到防治NASH的目的.     

己酮可可碱对非酒精性脂肪性肝炎大鼠肝脏核因子-κB信号通路及胰岛素抵抗的干预作用

目的观察己酮可可碱对非酒精性脂肪性肝炎大鼠肝脏核因子-kB（NF—kB）信号通路及胰岛素受体底物（IRS）-1、IRS-2和葡萄糖转运子2（GLUT2）表达的影响。方法24只SD大鼠高脂饮食饲养4周后，随机分为模型组和干预组，于实验第24周处死，并设普通饮食饲养大鼠6只作对照组。电泳迁移率分析检测肝脏NF—kB活性，Westernblot检测肿瘤坏死因子（TNF）α和KB抑制蛋白α（IkBα）表达，逆转录聚合酶链反应检测肝脏IRS—1、IRS12和GLUT2mRNA表达。结果与对照组相比，模型组肝脏NF-kB和TNFα显著增加，IkBα显著降低，伴IRS-2表达显著增加；与模型组相比，干预组NF—kB和TNFα显著降低，IkBα有所增高，而IRS-2表达显著减少；肝脏IRS—1和GLUT2表达在3组之间差异均无统计学意义。结论己酮可可碱可能通过影响肝脏NF—kB信号通路和增加肝细胞IRS-2表达，从而有助于改善非酒精性脂肪性肝炎大鼠肝脏胰岛素抵抗。     

Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis

BACKGROUND & AIMS: The increasing prevalence of nonalcoholic steatohepatitis (NASH) is due to the epidemic of obesity and type 2 diabetes, both of which are associated with insulin resistance. METHODS: To clarify the causal relationship between insulin resistance and the development of NASH, steatohepatitis was induced in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) and nondiabetic control Long-Evans Tokushima Otsuka (LETO) rats by feeding them a methionine and choline-deficient (MCD) diet. Insulin sensitivity of the rats was altered by adding a high-fat (HF) diet or the peroxisomal-proliferator activated receptor-gamma agonist pioglitazone to the MCD diet. RESULTS: The MCD diet-induced steatohepatitis was accelerated in OLETF rats after 8 weeks. Steatosis preceded inflammation, which led to fibrosis and the development of steatohepatitis. The hepatic gene expression for transforming growth factor-beta, alpha1 procollagen and plasminogen activator inhibitor-1 was up-regulated in OLETF rats compared with LETO rats. The MCD + HF diet further enhanced insulin resistance and led to rapid development of pre-cirrhosis in OLETF rats by increasing the triglyceride pool, activating stellate cells, and up-regulating gene expression for sterol regulatory element-binding protein-1c and fatty acid synthase in the liver. In contrast, pioglitazone attenuated the MCD diet-induced steatohepatitis in OLETF rats but not in LETO rats by reversing the underlying pathogenesis involved in this model through improvement of insulin resistance. These results confirm a link between insulin resistance and the development/progression of steatohepatitis, at least partly via up-regulation of genes for lipogenesis, inflammation, and fibrogenesis, in animal models. CONCLUSIONS: Insulin resistance and/or diabetes may accelerate the entire pathologic spectrum of NASH.     

Tranilast, an antifibrogenic agent, ameliorates a dietary rat model of nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease and is one of the most common liver diseases in the developed world. The histological findings of NASH are characterized by hepatic steatosis, inflammation, and fibrosis. However, an optimal treatment for NASH has not been established. Tranilast, N-(3',4'-dimethoxycinnamoyl)-anthranilic acid, is an antifibrogenic agent that inhibits the action of transforming growth factor beta (TGF-beta). This drug is used clinically for fibrogenesis-associated skin disorders including hypertrophic scars and scleroderma. TGF-beta plays a central role in the development of hepatic fibrosis, and tranilast may thus ameliorate the pathogenesis of NASH. We investigated the effects of tranilast using an established dietary animal model of NASH, obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and nondiabetic control Long-Evans Tokushima Otsuka (LETO) rats fed a methionine-deficient and choline-deficient diet. Treatment with 2% tranilast (420 mg/kg/day) for 8 weeks prevented the development of hepatic fibrosis and the activation of stellate cells, and down-regulated the expression of genes for TGF-beta and TGF-beta-target molecules, including alpha1 procollagen and plasminogen activator-1. In addition, tranilast attenuated hepatic inflammation and Kupffer cell recruitment, and down-regulated the expression of tumor necrosis factor alpha. Unexpectedly, tranilast ameliorated hepatic steatosis and up-regulated the expression of genes involved in beta-oxidation, such as peroxisome proliferator-activated receptor alpha and carnitine O-palmitoyltransferase-1. Most of these effects were observed in LETO rats and OLETF rats, which suggest that the action of tranilast is mediated through the insulin resistance-independent pathway. CONCLUSION: Our findings suggest that targeting TGF-beta with tranilast represents a new mode of therapy for NASH.     

饮食调整治疗大鼠非酒精性脂肪性肝炎

目的:观察单纯饮食改变治疗大鼠非酒精性脂肪性肝炎(NASH)的作用。方法:30只SD大鼠随机分为3组(每组n=10):正常组喂普通饲料;模型组喂高脂饲料;饮食治疗组在高脂饮食12周后恢复正常饲料喂养。16周后处死动物。结果:正常饮食能显著降低造模大鼠的体重、肝指数、转氨酶,还能改善肝脏脂肪变性和炎症坏死的程度。结论:单纯恢复正常饮食即可治疗大鼠NASH。     

Isolated idiopathic bile ductular hyperplasia in patients with persistently abnormal liver function tests

BACKGROUND/AIMS: Feeding mice a methionine choline deficient (MCD) diet serves as a nutritional model of non-alcoholic steatohepatitis (NASH). NASH and alcohol-induced steatohepatitis are histologically similar, suggesting a similar pathogenesis. Pentoxifylline (PTX) attenuates TNF-alpha production, acts as an antioxidant and decreases mortality in alcoholic steatohepatitis. The aim of our study is to determine if PTX attenuates MCD diet induced steatohepatitis and determine the mechanism of this effect. METHODS: Mice were placed on an MCD or control diet for 2 weeks and were treated with or without PTX. Serum ALT, liver histology, and inflammatory mechanisms were evaluated. RESULTS: PTX attenuates MCD diet induced steatohepatitis, decreasing both serum ALT levels and hepatic inflammation. Serum ALT levels were reduced approximately 50% in the MCD+PTX group compared to the MCD group. Hepatic glutathione levels were significantly higher in the MCD+PTX group compared to the MCD group. There was also a reduction in TNF-alpha mRNA in female mice treated with PTX. MCD+PTX mice had increased hepatic triglyceride content compared to the MCD mice, but less histologic evidence of inflammation despite the increased steatosis. Serum lipid and bile salt levels also were similar in PTX and vehicle control treated mice. CONCLUSIONS: PTX decreases serum ALT levels and hepatic inflammation in the MCD model of steatohepatitis, likely via increasing glutathione levels or reducing TNF-alpha expression.     

U230A芯片动态观察非酒精性脂肪性肝病大鼠肝脏基因表达

目的探讨大鼠非酒精性脂肪性肝病（NAFLD）发生过程中肝脏基因表达谱的改变。方法通过持续24周高脂饮食诱导大鼠NAFLD模型，应用U230A芯片检测不同造模时期肝脏基因表达，并设普通饮食饲养大鼠作对照。结果与对照大鼠相比，造模4周和8周时差异表达基因数分别为426条和540条，上调基因主要为细胞内磷酸化酶基因、代谢酶基因、脂肪酸结合蛋白基因，细胞色素P450基因以及细胞转录和分化基因等，下调基因主要为离子通道基因、激素受体基因、细胞黏附基因以及细胞骨架基因等；12周时差异表达基因有501条，其中表达上调352条，除上述基因外，还包括白细胞介素，Toll样受体4等炎症和凋亡相关基因；16周时差异表达的基因有665条，其中上调基因430条，炎症和凋亡相关基因表达进一步增加，且Ⅰ型胶原等纤维化相关基因出现表达上调，而细胞再生相关基因表达下调；24周时差异表达的基因有663条，其中上调基因512条，除上述基因表达差异外，主要包括成纤维细胞生长因子，转化生长因子和胰岛素样生长因子等纤维化相关基因。在所有表达差异的基因中，随着时间进展表达持续上调的基因共128条，其中成脂相关基因10条，代谢酶基因46条，炎症相关基因15条、凋亡相关基因10条，纤维化相关基因16条；持续下调的基因有52条，包括激素受体相关基因6条，细胞再生相关基因5条，电子转运基因11条等。结论高脂饮食大鼠肝脏基因谱呈动态改变，并与NAFLD的组织学进展一致。     

Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet

Recently, nonalcoholic steatohepatitis (NASH) was found to be correlated with cardiovascular disease events independently of the metabolic syndrome. The aim of this study was to investigate whether an atherogenic (Ath) diet induces the pathology of steatohepatitis necessary for the diagnosis of human NASH and how cholesterol and triglyceride alter the hepatic gene expression profiles responsible for oxidative stress. We investigated the liver pathology and plasma and hepatic lipids of mice fed the Ath diet. The hepatic gene expression profile was examined with microarrays and real-time polymerase chain reactions. The Ath diet induced dyslipidemia, lipid peroxidation, and stellate cell activation in the liver and finally caused precirrhotic steatohepatitis after 24 weeks. Cellular ballooning, a necessary histological feature defining human NASH, was observed in contrast to existing animal models. The addition of a high-fat component to the Ath diet caused hepatic insulin resistance and further accelerated the pathology of steatohepatitis. A global gene expression analysis revealed that the Ath diet up-regulated the hepatic expression levels of genes for fatty acid synthesis, oxidative stress, inflammation, and fibrogenesis, which were further accelerated by the addition of a high-fat component. Conversely, the high-fat component down-regulated the hepatic gene expression of antioxidant enzymes and might have increased oxidative stress. CONCLUSION: The Ath diet induces oxidative stress and steatohepatitis with cellular ballooning. The high-fat component induces insulin resistance, down-regulates genes for antioxidant enzymes, and further aggravates the steatohepatitis. This model suggests the critical role of lipids in causing oxidative stress and insulin resistance leading to steatohepatitis.     

Amelioration of Steatohepatitis with Pentoxifylline in a Novel Nonalcoholic Steatohepatitis Model Induced by High-Fat Diet

We sought to evaluate the effects of pentoxifylline (PTX) on steatohepatitis in a novel experimental nonalcoholic steatohepatitis (NASH) model induced by a high-fat diet (HFD). Thirty-three male Sprague-Dawley rats were randomly divided into 3 groups. The first group received only standard rat diet (control group); groups 2 (placebo group) and 3 were given HFD, ad libitum. After week 4, 0.5 mL of physiologic serum was injected subcutaneously to the placebo group and 50 mg/kg/d PTX was given intraperitoneally to the third group (group PTX). After 6 weeks all rats were humanely killed. Serum biochemistry, tumor necrosis factor-α (TNF-α), plasma, and liver tissue malondialdehyde (MDA) were analyzed. Histopathologically, steatosis, ballooning degeneration, inflammation, and fibrosis were determined. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, plasma and liver tissue MDA, and plasma TNF-α levels were significantly higher in placebo group than in the control group. Tumor growth factor-β levels, however, were comparable in the placebo and control groups. On histopathologic examination, steatosis, inflammatory cells per square millimeter, and ballooning degeneration were significantly higher in the placebo group than in the control group. No fibrosis or Mallory bodies were found in the placebo group. AST, ALT, plasma and liver tissue MDA, and plasma TNF-α levels were significantly lower in PTX group compared to the placebo group. Histopathologically, steatosis, mean number of inflammatory cells/mm² and ballooning degeneration in PTX group were also significantly lower than in the placebo group. In conclusion, PTX strikingly ameliorates steatohepatitis in this novel NASH model not only by inhibiting the TNF-α but also suppressing the oxidative stress markers.     

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

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.