肝细胞生长因子对慢性肝损伤时肝部分切除术后肝细胞影响的实验研究

目的：研究肝细胞生长因子对慢性肝损伤时肝部分切除术后肝再生和肝功能的影响。方法：本实验以四氯化碳和乙醇联合诱导慢性肝损伤模型,行30%肝部分切除术,术后10d,经腹腔注射肝细胞生长因子（分对照组、小剂量组、大剂量组）,同时建立正常对照组。观察不同剂量肝细胞生长因子对肝再生,肝功能和肝储备功能的影响。结果：①小剂量组与对照组的总蛋白、白蛋白、AST、ALT、总肝固醇、动脉血酮体比进行比较后,P＞0.05,小剂量的肝细胞生长因子无明显改善肝功能的作用。②大剂量组与对照组的AST、ALT、总胆固醇、动脉血酮体比进行比较后,P＜0.01,大剂量的肝细胞生长因子能显著改善肝功能。同时通过电镜和光镜观察,大剂量的肝细胞生长因子能促进肝再生。结论：①正常肝脏,或伴有慢性肝损伤的肝脏行部分肝功除术后,肝功能及肝储备功能,均有一定程度的,肝脏再生亦有障碍。②应用大剂量外源性肝细胞生长因子,维持一段时间,可明显改善肝功能和肝储备功能,促进肝细胞再生。     

rhGH对肝叶切除术后肝功能改善和肝脏再生作用的动物实验及临床研究

目的 探讨重组人生长激素（rhGH）对肝硬变肝叶切除术后肝功能改善和肝脏再生的作用。方法 建立SD大鼠肝硬变模型,然后行30％－40％肝切除,手术当天开始,实验组应用rhGH,对照组应用等量生理盐水代替,分别于术后第7、14及28天检测其肝功能、动脉血酮体比值（AKBR）、再生肝与体重的比值（RL／W）,并行光镜、电镜及肝细胞DNA图像分析。另外,将施行肝切除术的30例患者随机分为临床实验组和对照组,分别于术前1天、术后第1、14及28天测定其肝功能、血糖（Glu）、 胰岛素（RI）、前白蛋白（PA）及AKBR,记录两组患者术并发症发生率、肝功能衰竭发生率、平均住院时间。结果 动物实验组与对照组比较,AKBR值明显增高（P＜0．01）;术后第14及28天时的总蛋白和PA水平及肝细胞有丝分裂率明显升高（P＜0．05）;RL／W值也明显增高（P＜0．01）,肝细胞DNA浓度明显增高（P＜0．05）,双核再生肝细胞及面内质网也增多。临床实验组与对照组比较,术后第7及14天患者血清总胆红素、谷丙转氨酶和谷草转氨酶明显下降（P＜0．05）,血清白蛋白、PA、Glu、RI及AKBR明显升高（P＜0．05）。结论 肝硬变肝叶切除术后使用重组人生长激素,能使肝功能改善并促进肝再生。     

促肝细胞生长素对慢性肝损伤鼠肝部分切除术后肝细胞的影响

目的　 研究促肝细胞生长素 (主要成分为肝细胞生长因子 )对慢性肝损伤时肝部分切除术后肝再生和肝功能的影响。 方法　 以四氯化碳和乙醇联合诱导大鼠的慢性肝损伤模型 ,对其行 30 %肝部分切除术 ,术后 10d经腹腔注射促肝细胞生长素 (分对照组、小剂量组、大剂量组 ) ,同时建立正常对照组。观察不同剂量促肝细胞生长素对肝再生、肝功能和肝储备功能的影响。 结果　 小剂量组与对照组的总蛋白、白蛋白、谷丙转氨酶 (AST )、谷草转氨酶 (ALT)、总胆固醇、动脉血酮体比比较 ,差异无显著性 ( P >0 .0 5 )。大剂量组与对照组的AST ,ALT ,总胆固醇、动脉血酮体比的比较差异显著 ( P <0 .0 1)。电镜和光镜观察显示 ,大剂量的促肝细胞生长素能促进肝再生。 结论　 应用大剂量促肝细胞生长素可明显改善肝功能和肝储备功能 ,促进肝细胞再生     

内皮素对瘢痕成纤维细胞增殖和胶原合成作用的实验研究

目的：探讨内皮素（ET）在瘢痕成纤维细胞增殖与胶原合成中的作用及一氧化氮（NO）、粉防已碱（Tet）的拮抗效应。方法：体外培养人增生性瘢痕成纤维细胞，以^3H-TdR掺入法测定细胞增殖；以^3H-脯氨酸掺入量判断细胞胶原合成。结果：ET呈浓度依赖性促进瘢痕成纤维细胞增殖与胶原合成，随着ET浓度（2．5－100ng/ml）的增加，^3H-TdR掺入值较对照组分别增加了1．8、4．0和4．9倍；^3H－脯氨酸掺入值较对照组分别增加了1．1、3．1和3．8倍（P＜0．01）。用NO供体亚硝基乙酰青霉胺（S-nitroso-N-acetyl penicillamine,SNAP)50μg/ml单独处理成纤维细胞，对^3H-TdR掺入值无明显影响（与对照组相比，P＞0．05），但对^3H-脯氨酸掺入值有下调作用；SNAP可拮抗ET－1（25ng/ml）刺激细胞增殖作用（抑制率为22．89％，P＜0．05）；对ET－1的促胶原合成作用无明显影响（P＞0．05）。Tet在不抑制细胞DNA合成的药物浓度（3μg/ml）即可明显减少瘢痕成纤维细胞^3H-脯氨酸掺入值，并能显著降低由ET介导的瘢痕成纤维细胞^3H-TdR掺入值（抑制率为33．21％，P＜0．01）。结论：ET对体外培养的瘢痕成纤维细胞增殖与胶原合成具有显著促进作用，此效应可部分被SNAP、Tet所阻抗。     

肝再生刺激因子、表皮生长因子对肝细胞的作用

目的：观察肝再生刺激因子(HSS)及表皮生长因子（EGF）对肝细胞增殖再生作用合适剂量及其联合效应。并推测HSS作用时相。方法：以^3HTdR掺入法检测细胞DNA增殖；体外原代大鼠肝细胞培养不同时间加入HSS，MTT法检测细胞生长状况。结果与结论：1．HSS(≤100μg／ml)和EGF(≤100ng／ml)对肝衍生细胞均有显著刺激作用(P<0．01)，并存在剂量关系，但剂量过大，刺激作用反而下降。2．HSS、EGF存在协同作用，原代肝细胞、肝癌细胞株(SMMC．7721、BEL．7402)体外培养48h后，经(^3H)TdR掺入法检测cpm值分别为各自对照组的5．94，298和3．36倍。3．体外培养原代大鼠肝细胞，于贴壁后0h，20h加入HSS其刺激作用较40h组显著，提示HSS可能主要作用于肝细胞再生G1／S期。     

肝星状细胞对大鼠肝部分切除术后肝再生修复的影响

目的 探讨肝星状细胞（hepatic stellate cells,HSCs）在大鼠肝部分切除术后对肝损伤修复的影响.方法 体外实验部分：将大鼠肝星状细胞（HSCs）与大鼠肝细胞系（BRL-3A）共培养,CCK-8比色法检测细胞增殖情况;ELISA法检测培养肝星状细胞上清液中细胞因子,即肝细胞生长因子（hepatic growth factor,HGF）、胰岛素样生长因子（insulin growth factor,IGF）、表皮细胞生长因子（epidermal growth factor,EGF）、转化生长因子-α（transfactor growth factor-α,TGF-α）含量.体内实验部分;将45只260 ～330 g健康雄性SD大鼠随机分为三组：正常组（生理盐水组）、对照组（肝星状细胞培养液组）、实验组（肝星状细胞培养上清液组）.各组分别于肝大部切除术后第3、7、12天取血清检测肝功能情况并计算肝再生指数;HE染色切片显微镜下观察肝脏病理结构改变情况;免疫组织化学染色法检测增殖细胞核抗原（proliferating cell nucleus antigen,PCNA）、平滑肌肌动蛋白（α-smooth muscle actin,α-SMA）、甲胎蛋白（a1pha feta1 protein,AFP）及白蛋白（albumin,ALB）的表达情况.结果 ①CCK-8法检测肝星状细胞能促进肝细胞增殖（P＜0.05）;②上清液较培养液中细胞因子HGF、TGF-α含量多,差别有统计学意义（P＜ 0.05）;③实验组肝再生指数比对照组大,差别具有统计学意义（P＜0.05）;④实验组大鼠AST随着时间的推移,较对照组下降明显,差别有统计学意义（P＜0.05）;⑤实验组PCNA表达量较正常组、对照组增多,差别有统计学意义（P＜ 0.05）;⑥平滑肌肌动蛋白、白蛋白、甲胎蛋白三组间差别不显著（P＞ 0.05）.结论 ①体外肝星状细胞能促进肝细胞增殖;②肝星状细胞培养上清液能促进大鼠肝部分切除术后肝再生,其分泌的多种细胞因子在肝损伤再生修复中起了重要作用.     

微生物酵素对部分肝切除大鼠肝再生的作用

目的观察微生物酵素能否促进大鼠部分肝切除后肝再生。方法采用大鼠部分肝切除（Partial Hepatectomy,PH）模型,通过与对照组和促肝细胞生长素（Hepatocyte Growth-Promoting Factor,pHGF）组比较,在pH后12小时、24小时、48小时、72小时、120小时和168小时,留取相应肝组织,检测反映肝再生的指标肝再生率（Hepatic Regeneration Rate。HRR）、增殖指数（Proliferation Index,PI）和细胞增殖核抗原（Proliferating Cell Nuclear Antigen,PCNA）。结果在pH后12小时和24小时、微生物酵素组同促肝细胞生长素组一样与对照组相比,肝再生率高,差异有统计学意义（P〈0．05）;pH后12、24、72、120小时,微生物酵素组的PI高于对照组,差异有统计学意义（分别为P〈0．05、P〈0．01、P〈0．05和P〈0．05）。在pH后72小时和168小时PCNA出现高峰,微生物酵素组与对照组相比,差异有统计学意义（P〈0．05）。结论微生物酵素同促肝细胞生长素一样具有早期促进肝再生的作用。     

肝脏类器官构建及其对小鼠部分肝切除术后肝再生的作用#br#

目的 观察肝脏类器官对小鼠部分肝切除术后肝再生的作用。方法 体外构建肝脏类器官，通过形态学、PCR和免疫荧光对类器官进行初步鉴定。C57BL/6小鼠随机等分为对照组和治疗组，每组18只。对照组进行肝左叶、中叶切除术+肝包膜注射200 μL PBS；治疗组进行肝左叶、中叶切除术+肝包膜移植200 μL类器官悬液。建模成功后分别于术后第1、4、7天收集标本。通过血清生化检测、免疫组化和Western blotting评估肝脏类器官对小鼠肝部分切除术后肝再生的作用。结果 类器官体外培养3 d，从直径20 μm的囊性结构扩增到约125 μm的细胞团（P＜0.05），直径扩增近6 倍。肝脏干细胞标志基因EPCAM、SOX9和CK19明显上调（P＜0.05），传代前后基因保持稳定。免疫荧光显示CK8、Desmin、AFP和PCNA呈阳性。HE显示术后第4天，治疗组肝细胞形态大小基本恢复正常，形态较清晰，无炎症细胞浸润，无脂肪或气球样变。对照组小鼠肝细胞核仁染色加深，仍有炎性细胞浸润，部分区域存在肝细胞坏死区。免疫组化Ki67和Western blotting对增殖水平进行检测，结果显示治疗组增殖能力是对照组的3 倍。肝功能检测发现治疗组在术后第4天ALT、AST、TBIL和DBIL明显下降，ALB合成增加（P＜0.05）。结论 具有肝脏干细胞属性和增殖能力的肝脏类器官，能通过保护肝细胞、改善部分肝切除术后小鼠肝功能，发挥促进肝再生作用。     

大鼠肝切除术后肝损伤程度与肝再生状态的动态对比研究

目的：探讨肝切除术后肝损伤程度与肝再生状态的关系。方法：Wistar大鼠随机分为三组：（1）假手术组；（2）正常大鼠肝切除组；（3）肝硬化大鼠肝切除组，建立大鼠肝切除模型，观察围手术期血清和肝组织匀浆液中丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平、肝重／体重、肝再生率，以及应用免疫组化方法（SABC法）检测肝组织中增殖细胞核抗原（PCNA）的表达。结果：与正常大鼠相比，肝切除后肝硬化大鼠血清ALT和AST水平升高显著，持续时间较长（P＜0．05）；PCNA在肝切除后肝组织的表达显著延迟（P＜0．05），血清ALT和AST水平与肝再生率呈显著负相关（P＜0．05）。结论：肝损伤程度和肝再生状态呈负相关，肝损伤的程度影响肝再生状态，肝切除后检测血清ALT、AST水平的变化可以间接的了解肝再生情况。     

重组大鼠肝再生增强因子对肾小管上皮细胞增殖及凋亡的影响

目的探讨重组大鼠肝再生增强因子（rrALR）对体外培养的肾小管上皮细胞增殖及凋亡的影响。方法将体外培养的人肾小管上皮细胞株（HK2）分组，分别加入不同浓度的庆大霉素（GM）或（和）m～LR，^3H-胸腺嘧啶核苷（^3H-TdR）掺入法检测HK2细胞的增殖：吖啶橙／溴乙啶（AO／EB）染色和钙磷脂结合蛋白／碘化丙啶（annexin V／PI）双标记流式细胞术检测上述各组HK2细胞的凋亡。结果（1）rrALR对常规培养条件下的HK2细胞有直接的促增殖作用。并具有量效关系（在25ng／ml～50μg／ml的浓度范围内逐渐增强，P〈0．01）和时效关系（培养12h即有该作用，48h达到高峰，以后逐渐下降，P〈0．05）；（2）rrALR能够促进GM损伤后的HK2细胞增殖，有明显剂量依赖性（P〈0．05）；（3）rrALR呈剂量依赖性抑制GM诱导的HK2细胞凋亡（P〈0．01）。结论rrALR能够促进体外常规培养和GM损伤后的肾小管上皮细胞增殖．抑制GM诱导的小管上皮细胞凋亡，提示ALR可能对小管上皮细胞的中毒性损伤有改善作用。     

Beneficial effect of hyperbaric oxygenation on liver regeneration in cirrhosis

BACKGROUND: Underlying hepatic injury and cirrhosis are leading factors that interfere with the post-operative liver regeneration and function. Hyperbaric oxygenation (HBO) has been reported to ameliorate the ischemia-reperfusion injury of the liver, to induce compensatory hypertrophy of the predicted remnant liver in rats after portal vein ligation and to augment liver regeneration after hepatectomy in non-cirrhotic rats. Our aim was to determine the effect of HBO treatment on liver regeneration after partial hepatectomy in normal and cirrhotic mice in this experimental study. MATERIALS AND METHODS: The effect of HBO on liver regeneration was studied in a mice model combining carbon tetrachloride induced cirrhosis and partial hepatectomy. Mice were divided into four groups: Control, cirrhotic, non-cirrhotic HBO-treated, and cirrhotic HBO-treated. All animals underwent 40% hepatectomy. Liver regeneration was evaluated by the proliferating cell nuclear antigen-labeling index. Serum aspartate aminotransferase and alanine aminotransferase levels were measured to evaluate liver injury. RESULTS: Serum alanine aminotransferase and aspartate aminotransferase levels were significantly decreased in HBO-treated cirrhotic group compared to cirrhosis group after hepatectomy (P = 0.001 and P = 0.014, respectively). The proliferating cell nuclear antigen labeling index was significantly higher in HBO treated cirrhotic group than in cirrhotic group after hepatectomy (P = 0.022). CONCLUSIONS: Our results suggest that HBO treatment improves liver functions and augments hepatocyte regeneration in cirrhotic mice after hepatectomy. Post-operative HBO treatment may have a beneficial effect on post-operative liver function and regeneration in cirrhotic patients.     

Platelets Promote Liver Regeneration in Early Period after Hepatectomy in Mice

Background Platelets contain several growth factors, including platelet-derived growth factor and hepatocyte growth factor. Materials and methods We examined the effects of platelet increment on liver regeneration after 70% hepatectomy. Hepatectomies were carried out in male BALB/c mice, and subsequently divided into three groups: (i) untreated mice, (ii) thrombocytotic mice induced with thrombopoietin, and (iii) thrombocytopenic mice induced with anti-platelet antibody. Growth kinetics in the liver were analyzed as a function of the liver/body weight ratio, the mitotic index, the proliferating cell nuclear antigen labeling index and Ki-67 labeling index. Activation of signal transduction pathways relating to cell proliferation were examined, including the STAT3, Akt, and ERK1/2 pathways. Platelet accumulation in the residual liver was quantified by immunohistochemistry and transmission electron microscopy. Results In thrombocytotic and thrombocytopenic mice, liver/body weight ratios and Ki-67 labeling indices were significantly increased and significantly decreased, respectively, compared with untreated mice 48 hours post-hepatectomy. The Akt pathway was strongly activated, and platelet accumulation was significantly increased in thrombocytotic group 5 minutes post-hepatectomy compared with normal and thrombocytopenic groups. After hepatectomy platelets accumulated in the sinusoids of liver and promoted hepatocyte proliferation in early period after hepatectomy. Conclusion By increasing or decreasing the platelet, marked changes in liver regeneration can occur, due to differences in cellular signaling and mitosis.     

Expression of anti-apoptotic protein, Bcl-2, in liver regeneration after a partial hepatectomy

BACKGROUND: Although Bcl-2 is well known to have anti-apoptotic activities in vitro and in vivo, the role of Bcl-2 relating to liver regeneration remains controversial. The aim of this study was to document the effect of Bcl-2 expression on liver regeneration in rats undergoing a partial hepatectomy. MATERIAL AND METHODS: Adult male Wistar rats (n = 4/group) at 72 h before undergoing a 70% partial hepatectomy (PH) were administered 1 x 10(9) plaque-forming units of adenovirus vector encoding either human Bcl-2 (group 1) or LacZ (group 2) intravenously and were sacrificed at 0, 12 h, and at 1, 2, 3, 7, 14, and 21 days postoperatively. In group 3, normal saline was injected instead of adenovirus vector. Liver regeneration was monitored by measuring the restituted liver mass and proliferating cell nuclear antigen (PCNA) immunostaining. The incidence of apoptosis in the liver was analyzed by the immunohistochemical detection of single-stranded DNA at 14 and 21 days postoperatively. RESULTS: The restituted liver mass showed significantly higher values in group 1 (26.1 +/- 7.2%) than in group 2 (14.7 +/- 6.8%) and 3 (13.6 +/- 5.0%) at 1 day after PH (P < 0.05). The PCNA labeling index was significantly higher in group 1 (47.2 +/- 9.9%) than in groups 2 (19.0 +/- 7.8%) and 3 (19.2 +/- 15.2%) at 1 day after a partial hepatectomy (P < 0.05). The hepatocyte growth factor (HGF) mRNA expression was significantly lower in group 1 than in group 2 at 12 h after PH (P < 0.05). The number of single-stranded DNA-positive cells decreased significantly more in group 1 (5.67 +/- 1.53 positive cells/10 fields per tissue) than those in group 2 (18.33 +/- 7.57 positive cells/10 fields per tissue) at 14 days after PH. CONCLUSIONS: These results thus indicated that an overexpression of anti-apoptotic protein Bcl-2 does not necessarily have an anti-apoptotic effect on liver regeneration but appears to have a pro-proliferative effect in the early phase of liver regeneration.     

In vivo 31P NMR spectroscopic changes during liver regeneration

Liver regeneration following partial hepatectomy involves rapid cell division 24 to 72 hr postresection. This cell division would necessarily involve changes in intracellular energy stores and cell membrane phospholipid precursors. In tumor models 31P nuclear magnetic resonance (NMR) has been shown to identify intracellular substrate changes associated with cell growth. The ability to monitor early changes in adenosine triphosphate (ATP), inorganic orthophosphate (Pi), phosphomonoesters (PME), or phosphodiesters (PDE) after liver resection could indicate the intracellular changes necessary for hepatocellular regeneration. In vivo 31P NMR scans of the liver were performed in both normal rats and in rats at 24, 48, 72, and 120 hr after 70% hepatectomy. At 48 hr, total ATP fell to 18.9% (P less than 0.05) and both Pi/beta-ATP and PME/beta-ATP were significantly elevated (P less than 0.01) from controls. These changes correlate with the known mitotic peak in the rat following hepatectomy. We conclude that in vivo 31P NMR is a potentially valuable tool for studying hepatic regeneration. The data also suggest that hepatocellular regeneration may be critically dependent on cellular ATP stores.     

肝切除时门静脉血部分动脉化的研究

目的 研究犬门静脉血部分动脉化的肝保护作用。方法 建立大保留肝（占全肝６０％）暂时性血流阻断、肝固有动脉切断并切除未阻断肝的急性肝衰模型（对照组）,并行肝总动脉与胃十二指肠静脉吻合（Ａ－Ｐ组）,观察生存率并定时测定丙氨酸转氨酶（ＡＬＴ）、动脉血酮体比（ＡＫＢＲ）及肝动脉脉、门静脉血气分析。结果 对照组７天生存率为３７．５％,Ａ－Ｐ组均较差异有非常显著性（Ｐ〈０．０１）,门静脉和肝静脉血氧分压均较术     

Effects of human hepatocyte growth factor on the proliferation of human hepatocytes and hepatocellular carcinoma cell lines

BACKGROUND: Hepatocyte growth factor (HGF) has been suggested to initiate both hepatocyte and tumor cell proliferation after partial hepatectomy, thereby supporting local tumor recurrence. The aim of this study was to clarify the role of HGF in the regeneration of human hepatocyte and the growth of residual hepatocellular carcinoma cells after liver resection. PATIENTS/METHODS: 36 patients who underwent partial hepatectomy for hepatocellular carcinoma (HCC) or living liver donation have been analyzed for HGF serum levels at day -1 through day 5 following surgery using an enzyme-linked immunosorbent assay. Isolated human hepatocytes and HCC cell lines (Hep 3B, Hep G2) were treated either with recombinant human (rh)-HGF, or sera from the 36 patients in the presence or absence of anti-HGF in order to measure their proliferative capacity using (3)H-thymidine incorporation. RESULTS: Basal HGF levels were significantly higher in HCC than in healthy patients (1,573 +/- 131 vs. 778 +/- 64 pg/ml; p < 0.001), however, the postoperative rise of HGF in healthy patients was higher (9,608 +/- 3111 vs. 2,060 +/- 148 pg/ml) than in HCC patients. Incubation of human hepatocytes and Hep 3B cells with rh-HGF revealed a dose-dependent increase in DNA synthesis, while anti-HGF partially abolished this effect. Sera from normal and resected HCC patients stimulated DNA synthesis only in human hepatocytes, whereas it was inhibited in HCC cell lines. CONCLUSION: HGF plays an important role in hepatocyte proliferation but contrary to in vitro results, HGF does not play a major role for the progression of hepatocarcinoma cells in vivo.     

Anabolic steroid nandrolone augments hepatic regenerative response in rats

The success of recovery after liver resection depends on the regeneration and functions of the remnant liver. In this study we investigated whether liver regeneration was facilitated by nandrolone decaonate after two-thirds partial hepatectomy in rats. Study animals were pretreated with nandrolone (5 mg/kg), while control animals received a placebo. Animal were sacrificed at 12, 24, 48, and 72 hours. We compared the survival rates, liver function tests as well as the amount of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine-biotin nick end labeling assay, and regeneration, which was expressed as ratio of proliferating cell nuclear antigen and restoration ratio. A significant increase in hepatocyte regeneration at 24 and 48 hours in partially hepatectomized rats treated with nandrolone decaonate was observed compared to controls. This observation was confirmed by the significant acceleration of the liver restoration rate, which was 1/5 faster than in partially hepatectomized controls. The results of this study indicate that liver regeneration in rats treated with nandrolone show a prompt, faster regeneration after partial hepatectomy.     

Famotidine does not inhibit liver regeneration

The H2-blockers, cimetidine and ranitidine, are reported to inhibit liver regeneration. In this work, the effects of a new powerful H2-receptor antagonist, famotidine, on liver regeneration were studied in rats. The animals were divided into three groups: group I in which a standard two-thirds hepatectomy was performed, group II in which the rats were treated with famotidine (intramuscular dose of 0.8 mg/kg body weight) on the day of operation and 24 and 48 h after hepatectomy, and group III in which the animals were intramuscularly injected with a larger dose of famotidine (1.2 mg/kg body weight) in the same way as group II. The histology and mitotic index of remnant livers and serum levels of aminotransferase and albumin were examined from 24 h to 10 days after the operation. The treatment with famotidine (groups II and III) did not inhibit hepatocyte mitosis but, on the contrary, raised the index on day 3 after hepatectomy when compared with the controls (group I). The albumin synthesis was well preserved in the famotidine-treated animals. The noninhibitory effects of famotidine on liver regeneration are discussed.