Portal blood flow regulates volume recovery of the rat liver after partial hepatectomy: molecular evaluation

BACKGROUND/AIM: Liver regeneration is a finely tuned process that is closely regulated by multiple cell cycle steps. Although the portal blood flow affects liver regeneration, the molecular mechanism by which the blood flow regulates gene expression and liver function is largely unknown. The aim of this study was to investigate the molecular effect of portal blood flow on hepatocyte proliferation and gene regulation during liver regeneration. MATERIALS AND METHODS: We developed a simple surgical rat model to investigate the relation between portal blood flow and liver regeneration by partially ligating the portal trunk with 8-0 Proline sutures under microscopy to reduce the blood flow by 40%. We investigated recovery of liver volume, DNA synthesis, and gene expression associated with cell cycle regulators, comparing partially hepatectomized (PH) rats without (PH group; n = 30) and with partial portal ligation (PHPL group; n = 30) for 7 days after the operation. RESULTS: The hepatic tissue blood flow and the recovery ratio between liver weight and body weight in the PHPL group were significantly lower than in the PH group after hepatectomy. The peak 5-bromo-2'-deoxyuridine labeling index in the PHPL group was delayed and weak compared with the PH group. The expression of CT-1 and cyclin D, E, and B mRNAs indicated that the liver regeneration in the PHPL group was delayed and weak. In addition, there was reciprocal expression of C/EBPalpha and C/EBPbeta mRNAs, an observation supported by their nuclear protein levels. Furthermore, the cytochrome P-450 protein level in the PHPL group was higher than that in the PH group 1 day after hepatectomy. CONCLUSION: The portal blood flow regulates the activity of liver regeneration and the gene expression associated with cell cycle regulators, while the functions are maintained.     

Further studies on hepatic stimulatory substance (SS) after partial hepatectomy

The stimulatory substance (SS) that is found in the cytosol of regenerating dog livers and which promoted regeneration when injected into the portal vein after Eck fistula did not cause glomerular proliferation when active cytosol was injected into the renal artery. The finding was compatible with but did not prove organ specificity of hepatic SS. The development of SS was completely prevented by extirpation of all nonhepatic splanchnic organs at the same time as partial hepatectomy. This finding indicated that SS in the cytosol donors was a feature rather than an initiator of regeneration, and one that depended upon the collaboration of extrahepatic (including splanchnic hepatotrophic) factors.     

Kupffer cell-mediated inhibition of liver regeneration after combined hepatectomy and pancreatectomy

Recently, simultaneous hepatectomy and pancreatoduodenectomy has been performed for the treatment of some biliary tract cancers in Japan. Postoperative hepatic failure is a common and potentially fatal complication. The aim of this study was to examine the reduction in the rate of liver regeneration after 70% hepatectomy (Hx) alone or in combination with 70% pancreatectomy (HPx). Male Sprague-Dawley rats underwent hepatectomy or simultaneous hepatectomy and pancreatectomy. The ratio of liver weight to body weight, the labeling index of hepatocytes in vivo, and DNA synthesis of the hepatocytes and/or Kupffer cells in primary culture were analyzed. The ratio of liver weight to body weight and the labeling index in HPx rat were found to be significantly lower than those values in Hx rats. There were no significant differences in plasma alanine aminotransferase levels between the two groups. The inhibitory effect on DNA synthesis was observed with coculture of hepatocytes and Kupffer cells when the portal plasma obtained 1 hour after operation was added. We further observed that the conditioned medium of Kupffer cells stimulated by the addition of the portal plasma that was obtained 1 hour after HPx inhibited DNA synthesis of hepatocytes. This effect was abolished after incubation at 56° C for 30 minutes. These results strongly suggest the existence of a growth inhibitory factor in portal plasma after HPx. This heat-labile growth inhibitory factor was released from Kupffer cells and would appear to act on hepatocytes in a paracrine manner. Supported by the Kanae Foundation for Life and Sociomedical Science, Japan. Presented at the Thirty-Eighth Annual Meeting of The Society-for Surgery of the Alimentary Tract, Washington, D.C., May 11–14, 1997.     

Possible inhibitory mechanism of liver regeneration through non-parenchymal cells after combined hepatectomy and pancreatectomy

BACKGROUND: Recently, simultaneous hepatectomy (Hx) and pancreaticoduodenectomy have been performed in the treatment of biliary tract cancer. Postoperative hepatic failure is a common and potentially fatal complication. The aim of this study was to examine the reduced rate of liver regeneration after 70% Hx alone or in combination with 70% pancreatectomy (HPx). MATERIALS AND METHODS: Male Sprague-Dawley rats underwent Hx or combined Hx and Px. The ratio of liver-body weight, labeling index of hepatocytes in vivo, and DNA synthesis of hepatocytes and/or Kupffer cells in primary culture were analyzed. RESULTS: The ratio of liver-body weight in HPx rats was found to be significantly lower than that in Hx rats from 12 hours to 72 hours after surgery. There was no difference in blood glucose or ALT levels between the two groups. An inhibitory effect on DNA synthesis was observed in cocultured hepatocytes and Kupffer cells when portal plasma obtained one hour after surgery was added. We further observed that conditioned medium of Kupffer cells stimulated by portal plasma obtained one hour after HPx inhibited DNA synthesis by hepatocytes. This effect was abolished after incubation at 56 degrees C for 30 min. CONCLUSIONS: These results clearly indicate the existence of a growth inhibitory factor in portal serum after HPx. This heat-labile growth inhibitory factor was released from Kupffer cells stimulated by portal plasma after HPx and appears to act on hepatocytes in a paracrine manner.     

Characteristics of hepatocytes derived from early ES cells and treatment of surgically induced liver failure rats by transplantation

BACKGROUND: Although liver transplantation has become a standard therapy for diseases such as fulminant hepatitis and cirrhosis, the lack of donor organs remains a major problem. One solution is the development of transplantable hepatocytes. The metabolic characteristics as well as function and adaptation of hepatocytes (R-EES-hep cell) derived from rat early embryonic stem cells were examined after transplantation into rats with surgically induced liver failure. METHODS: Rat hepatocyte cell lines were established from early embryonic stem cells cultured in the presence of embryotrophic factors by colony cloning methods. The cell lines were established from two cell embryos taken from spontaneous dwarf rats using the novel method of Ishiwata et al. Morphologic differentiation as well as albumin and bilirubin production were observed by immunostaining. R-EES-hep cells were transplanted into the spleens of 90% hepatectomized, surgically induced liver failure rats to analyze survival rates. RESULTS: When cultured in type I collagen gel the cells formed cordlike structures resembling the liver. Both albumin and bilirubin production were observed when transplanted; the spleen was converted into a liver-like structure with prolonged survival of the 90% hepatectomized rats for up to 3 months up to the time of killing. CONCLUSIONS: R-EES-hep cells showed many of the distinctive metabolic characteristics of the liver. These cells may be efficient for further research and application for hepatic cell transplantation to treat liver insufficiency patients and as biologic artificial organs.     

Delayed liver regeneration with negative regulation of hepatocyte growth factor and positive regulation of transforming growth factor-beta1 mRNA after portal branch ligation in biliary obstructed rats

BACKGROUND: The influence of obstructive jaundice on liver regeneration is still controversial. The aim of this study was to investigate liver regeneration after portal branch ligation (PBL) in the jaundiced rat, focusing on hepatocyte growth factor (HGF) and transforming growth factor-beta1 (TGF-beta 1). METHODS: Male Wistar rats underwent PBL or a sham operation 7 days after a common bile duct ligation. Liver wet weight, proliferating cell nuclear antigen labeling, HGF and TGF-beta 1 mRNA expression, and immunohistochemical staining with alpha-smooth muscle actin antibody were studied. RESULTS: The rate of liver regeneration in jaundiced liver was decreased as compared to a non-jaundiced liver. DNA synthesis in the jaundiced non-ligated lobe was significantly lower than in the non-jaundiced liver as was the peak level of HGF mRNA expression after PBL. In contrast, the level of TGF-beta 1 mRNA expression was higher in the jaundiced liver, and alpha-smooth muscle actin staining showed that hepatic stellate cells were gradually activated into myofibroblast-like cells. CONCLUSIONS: Obstructive jaundice decreased the expression of HGF mRNA and increased the expression of TGF-beta 1 mRNA, resulting in delayed liver regeneration after PBL. We suggest that hepatic stellate cells activated in obstructive jaundice may affect the expression of these growth factors.     

The characterization and partial purification of hepatocyte proliferation factor.

This report presents further evidence that the liver is the source of the factor responsible for the initiation and/or stimulation of hepatic regeneration. Initial experiments for the isolation and characterization of the active factor are presented. The factor was isolated from the cytosol of regenerating livers (RLC). After an in vivo exposure to RLC, hepatocytes were pulsed in vitro with 3H-thymidine to measure DNA synthesis. Rat and porcine RLC stimulated DNA synthesis in hepatocytes isolated from growing (nonhepatectomized) livers of weanling rats, or from regenerating livers of adult rats. The ability of porcine RLC to stimulate hepatocyte DNA synthesis demonstrated that the factor responsible was not species-specific. In contrast, normal non-regenerating liver cytosol did not stimulate hepatocyte DNA synthesis. Further experiments also revealed that the factor is heat stable. The activity responsible for the increased DNA synthesis was called hepatocyte proliferation factor (HPF). The assay for detecting HPF activity in the nonhepatectomized recipient will facilitate further characterization and purification of HPF.     

Effect of portal hemodynamics on liver regeneration studied in a novel portohepatic shunt rat model

BACKGROUND: The role of portal hemodynamics on liver regeneration after partial hepatectomy is not fully understood. The aim of our study was to characterize the effects of portal hemodynamics using a novel rat model. METHODS: We established a rat model of a portohepatic shunt with a 70% hepatectomy (PHS model), in which the portal pressure remained stable during and after the 70% hepatectomy. To assess the effect of portal hemodynamics on liver injury and regeneration in the first 24 hours, we compared PHS rats with those with a simple 70% hepatectomy. RESULTS: Biochemical and histopathologic changes were similar between the 2 groups. Liver weight increased in the control, whereas it did not in the PHS group (P = .0021). Hepatocytes were enlarged in the control but not in the PHS group, although DNA synthesis was similar in both groups. Apoptotic hepatocytes increased markedly in PHS at 24 hours, whereas minimal apoptosis was noted throughout the course of the study in the control group. Hepatocyte growth factor increased similarly, except that it was not activated in PHS. CONCLUSIONS: Our results suggested that a portal hyperdynamic state early after a 70% hepatectomy was necessary for liver regeneration through activation of hepatocyte growth factor, promoting hepatocyte hypertrophy and avoiding apoptosis, while DNA synthesis in hepatocytes was independent of portal hemodynamics.     

Effect of partial portal vein ligation on hepatic regeneration

To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p less than 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p less than 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection.     

Characterization of certain hepatocyte-proliferating and/or protective factors induced by the sensitization of freezing-thawing hepatic tissue

Although tumor cryosurgery would be expected to produce beneficial immunological effects from the enhancement of anti-tumor activity, under certain conditions the tumor may become enlarged and metastases promoted due to increased immunosuppressive activity and a high zone tolerance. In the present study, we examined whether hepatocyteproliferating factors were produced by the inoculation of freezing-thawing hepatic tissue (FTHT). Serum obtained from rats inoculated with FTHT increased DNA synthesis, according to measurement by [³H]thymidine incorporation in primary cultured rat hepatocytes. This increase was dependent on the serum concentration, with serum obtained on day 14 after the inoculation being the most potent for hepatocyte proliferation. The sensitized serum promoted DNA synthesis nearly as much as serum obtained from a 70% hepatectomized rat, but slightly less than 10ng/ml hepatocyte growth factor. The sensitized serum also protected hepatocytes from carbon tetrachloride (CCI₄)-induced hepatotoxicity. Optical density measured by the 3-(4,5-dimethyl-thiazole-2-yl)-2,5-diphenyl tetrozolium bromide (MTT) cytotoxicity assay was increased, and the release of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in medium was decreased by treating hepatocytes damaged by CCI₄ with the sensitized serum. These results suggest that certain hepatocyte-proliferating and protective factors are induced in serum by the inoculation of freezing-thawing hepatic tissue, and that the sensitized serum may be useful in the treatment of liver failure.     

Transforming growth factor-alpha (TGF-alpha) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats.

Impaired liver regeneration in cirrhosis complicates the surgical treatment of liver tumors which arise in this setting. We developed a rat model to investigate the regenerative response of cirrhotic liver after hepatectomy and studied the effect of exogenous transforming growth factor-alpha (TGF-alpha), a potent liver mitogen. Micronodular cirrhosis was established by the simultaneous administration of CCl4 and phenobarbital. Hepatic DNA synthesis ([3H]thymidine incorporation into DNA) 24 hr after partial hepatectomy in cirrhotic rats was 15.6 +/- 3.4 cpm/micrograms DNA (means +/- SEM), which was significantly lower than in normal rats (37.3 +/- 3.4 cpm/micrograms DNA, P less than 0.05). Exogenous TGF-alpha (30 nmol/kg, sc every 12 hr) significantly improved [3H]thymidine incorporation (35.6 +/- 8.2 cpm/micrograms DNA, P less than 0.05). An autoradiographic nuclear labeling index also confirmed increased DNA synthesis (6.7% vs 13.4%). TGF-alpha had no effect on normal regenerating liver (42.5 +/- 8.8 cpm/micrograms DNA, NS). Although the significance of TGF-alpha-enhanced liver regeneration in cirrhosis has yet to be assessed, this model may be useful for the study of mechanisms which control hepatic proliferation.     

Effect of activation of the reticuloendothelial system on hepatocyte regeneration in partially hepatectomized rats

Enhanced effect on rat hepatocyte regeneration through activation of the reticuloendothelial system (RES) was investigated. RES was activated using by OK-432 and the phagocytic activity (K-value) increased 2-fold over control rats 24 hours after intraperitoneal injection of OK-432. In OK-432 treated rats, the amount of cyclic AMP in the regenerating liver also increased 1.5-fold higher than in control rats 14 hours after hepatectomy. After 70% partial hepatectomy, liver DNA synthesis in OK-432 treated rats increased 2 to 5-fold higher than in control rats. There was a good correlation between the K-value before hepatectomy and DNA synthesis 24 hours after hepatectomy (r = 0.96). Therefore the RES is one of the most important regulatory factors in liver regeneration. Augmentation of RES before hepatectomy may prevent hepatic failure after resection in liver diseases.     

Effect of splenectomy on liver regeneration and polyamine metabolism after partial hepatectomy

The effect of splenectomy on hepatic ornithine decarboxylase (ODC) induction, DNA synthesis, and mitosis of hepatocytes was studied in rat liver after partial hepatectomy. ODC activity markedly increased in the early stages of liver regeneration, and the increase in the activity was significantly enhanced in splenectomized rats. Splenectomy specifically induced ODC since tyrosine aminotransferase and general protein synthesis were not affected. Splenectomy also enhanced increase in hepatic polyamines, DNA synthesis, and mitosis in regenerating liver. The results suggest that splenectomy affects liver regeneration after partial hepatectomy by enhancing induction of ODC activity, which is an important biochemical event in the early stage of liver regeneration.     

Changes in hepatic venous oxygen saturation related to the extent of regeneration after partial hepatectomy in rats

BACKGROUND: Changes in hepatic oxygen metabolism in relation to the extent of liver regeneration are expected after partial hepatectomy. There are few reports, however, about hepatic oxygen metabolism during liver regeneration. In this study, we evaluated changes in hepatic oxygen metabolism related to the regeneration rate, and the relationship between hepatic venous oxygen saturation (Shvo2) and liver regeneration after partial hepatectomy. METHODS: The work was done using 50% hepatectomized rats with continuous infusion of octreotide for inhibition of liver regeneration or with saline as control. The hepatic hemodynamics, oxygen metabolism, and Shvo2 levels as well as the regenerating liver status were evaluated for 3 days after hepatectomy. RESULTS: Administration of octreotide resulted in a significant reduction of the regenerating liver weight on days 1 and 3 after hepatectomy compared with the control group. Significantly decreased DNA synthesis and proliferating cell nuclear antigen labeling index were also found on day 1. Meanwhile, hepatic oxygen consumption (HVO2) and oxygen extraction ratio were significantly decreased in the octreotide-treated group on day 1. In contrast, the Shvo2 levels in the octreotide-treated group were significantly higher than those in the control group, and were inversely correlated with the HVO2. CONCLUSION: The remnant liver demands an increased amount of oxygen in relation to the extent of regeneration, and changes in the Shvo2 are inversely correlated with the HVo2. Therefore, monitoring the Shvo2 could be useful for estimating liver regeneration after partial hepatectomy.     

Flow cytometric analysis of hepatocellular regeneration after partial hepatectomy and administration of hepatotrophic factors

Kinetics of hepatocellular regeneration after 30% and 70% hepatectomy and the effect of hepatotrophic factors on the normal liver and regenerating livers after hepatectomy were investigated by flow-cytometric analysis using adult male rats. The results were as follows: The DNA histogram of hepatocytes in the normal group had two peaks in G0G1 and G2M components; G0G1 29% S 13%, G2M 58%. In the 30% hepatectomized group, the peak of G2M slightly increased, and remarkable change was not noticed during 4 weeks. In the 70% hepatectomized group, the percentage of hepatocytes in G0G1 and G2M were markedly changed during 2 days after hepatectomy. The peak of G0G1 moved to S after 24 hours, to G2M after 36 hours and returned to G0G1 after 48 hours. Afterwards the G0G1 gradually decreased while the G2M increased and they finally reached a single peak of G2M at the 7th day. Supernatant of the intestinal homogenate after hepatectomy and EGF initiated the cell kinetics in normal and regenerating rat livers. Changes on cell kinetics was not observed after insulin and glucagon administration.     

内皮素在肝外型门静脉高压症发病机制中的作用

目的 探讨内皮素在门静脉高压症发病机制中的作用及其可能的机制。方法 参照Benoit方法建立大鼠门静脉高压症模型,应用放射免疫学方法分别测定门静脉高压症组、正常对照组和假手术组大鼠血浆及肝组织中ET－1的含量,并观察ET－1和ETA受体拮抗剂对门静脉高压症大鼠FPP以及体外培养的门静脉血管平滑肌细胞（VSMC）增殖和蛋白质合成的影响。结果 ①门静脉高压症大鼠血浆和肝组织ET－1含量显著高于正常对照组和假手术组（P＜0．01）;②静脉注ET－1可以显著提高门静脉高压症大鼠的自由门静脉压（P＝0．002）,静注ETA受体拮抗剂则可以显著降低门静脉高压症大鼠的FPP（P＝0．047）;③ET－1可以显著剂量依赖性地促进门静静脉VSMC对^3H-TdR和^3H-Leu的掺入,这种作用可以被ETA受体拮抗剂所抑制。结论 ①ET－1可以通过ETA受体介民垢缩血管作用,增加肝内门静脉系统血流阻力的功能性部分;②ET－1可以显著促进体外培养的大鼠门静脉血管平滑肌细胞的增殖和蛋白质合成,参与门静脉系统的血管增生－血管重构,并影响门静脉系统血流阻力的器质性部分;③门静脉高压症大鼠体内ET－1的过量表达通过影响门静脉系统血流阻力的功能性部分和器质性部分,在门静脉高压症的发病机理中具有重要作用。     

Enhancement of portal blood flow by ursodesoxycholic acid in partially hepatectomized rats

Portal venous flow (PVF) was examined after portal injection of ursodesoxycholic acid (URSO) in rats that were partially hepatectomized by either 40% or 66%. URSO (10 mg/kg per minute) was injected into the portal vein and was thereafter observed to increase PVF concomitantly with a fall in portal venous pressure (PVP) in control animals. The increase in PVF in response to URSO was dose-dependent. In hepatectomized rats, the PVF response was augmented when the same dose of URSO was portally injected, and the magnitude of response was enhanced in proportion to the volume of liver resected. These results suggest that URSO increases PVF through vasodilation of the portal vessels, and therefore URSO is considered to increase PVF potently in a partially hepatectomized condition.     

Auxiliary partial liver grafting in rats: effect of host hepatectomy on graft regeneration,and review of literature on surgical technique

Auxiliary partial liver transplantation (APLT) is beneficial for fulminant liver failure when there is potential for recovery of the diseased liver. However, the impact of host hepatectomy on regeneration of the grafted liver is unclear. In this study, we modified a previous rat model of auxiliary whole liver transplantation without portal vein reconstruction, and studied the effect of host hepatectomy on regeneration of the cut liver graft. Thirty percent of the liver was heterotopically transplanted, to connect the recipient's left renal artery and vein with the graft's aortic cuff of the hepatic artery and inferior vena cava, respectively, using a cuff technique; 30% of the recipient liver then was cut. The control group was left intact. The liver grafts were weighed preoperatively and 2 weeks postoperatively. This procedure prevented congestion of the graft liver and achieved a high success rate, even when performed by a surgeon who was relatively inexperienced with the technique. The weight of the grafted liver in the host hepatectomized group significantly increased (P < 0.05) compared with that of the control group. We developed an experimental model of APLT and reviewed the literature on rat heterotopic liver transplantation, and compared the surgical techniques.     

Inhibition of hepatic DNA synthesis after partial hepatectomy in the rats with obstructive jaundice with special reference to the enhancement of hepatic protein synthesis

We studied the liver regeneration after partial (68%) hepatectomy in rats with obstructive jaundice followed by the relief of obstruction. Rats received bile duct ligation, then 5 or 14 days later choledocho-duodenostomy was performed. Partial hepatectomy was done at various intervals after the relief of obstruction. DNA synthesis of the regenerating liver, hepatic protein synthesis and mitochondrial swelling induced by exogenous phospholipase A2 (PLA2) were determined. Hepatic DNA synthesis was significantly inhibited in obstructive jaundiced rats compared to controls. While the inhibition disappeared 5 days after the relief of obstruction in 5-day-obstructed group, it was still detectable as late as 21 days after the drainage in 14-day-obstructed group. Hepatic protein synthesis was markedly increased by obstructive jaundice, and this increase continued until 10 days after drainage in 14-day-obstructed group. Partial hepatectomy also increased the hepatic protein synthesis significantly in normal rats, but failed to show any significant changes in obstructive jaundiced rats. Any difference could not be found in PLA2-induced hepatic mitochondrial swelling between obstructive jaundiced rats and normal rats. We concluded the preceding energy-requiring responses in obstructive jaundiced liver resulted in the reduction of hepatic DNA synthesis and in the lack of additional increase of hepatic protein synthesis as the responses to a further insult of partial hepatectomy.     

门静脉分支结扎后门静脉压力变化与肝再生的关系

目的 探讨90%门静脉分支结扎后大鼠门静脉压力变化与肝再生的关系.方法 45只雄性SD大鼠行90%门静脉分支结扎术,其中5只进行假手术作为对照.观察不同时相点门静脉压力和非结扎侧肝脏质量变化,光学显微镜下观察非结扎侧肝细胞的形态学变化,免疫组织化学方法检测未结扎侧肝细胞的增殖细胞核抗原(PCNA),TUNEL法检测未结扎侧肝细胞的凋亡情况,并进行定最分析.采用Pearson相关分析和t检验分析数据.结果 95%(38/40)的大鼠存活.结扎侧肝叶进行性萎缩,非结扎侧肝叶占全肝质量的比例随时问推移而增加,12 h内增加较缓慢,仅为10.75%;而1～5 d则增加速度明显加快,达到27.57%;7～28 d达到平台期,缓慢增加到32.37%.术前门静脉压力为(9.1±1.8)cm H_2O(1 cm H_2O=0.098 kPa);结扎后立即升高,12 h达到高峰(15.8±2.7)cm H_2O,与术前比较差异有统计学意义(t=6.847,P<0.05);1～28 d由(13.6±2.3)cm H_2O逐渐下降为(9.3±2.0)cm H_2O.术前大鼠PCNA阳性细胞计数为7%±3%,术后12 h至3 d由14%±5%上升至21%±6%,第5天达到高峰为26%±7%,与术前比较差异有统计学意义(t=9.129,P<0.05),随后逐渐恢复正常.TUNEL法检测结果显示,术前大鼠肝脏和术后各时相点大鼠未结扎侧肝脏仅见极少量凋亡细胞.大鼠门静脉压力与非结扎侧肝叶肝细胞PCNA的表达在术后1、3、5 d呈正相关(r=0.913,0.896,0.908,P<0.05),在术后14 d时相点呈负相关(r=-0.926,P<0.05).结论 大鼠90%门静脉分支结扎术后,引起未结扎侧肝细胞的活跃再生,再生后的肝脏可恢复原来的质量;肝再生以肝细胞增殖加速为主,而非肝细胞凋亡减少;门静脉压力变化在肝再生过程中可能发挥重要作用.