细胞因子在肝脏再生过程中的调控作用

在生理、外伤、感染或毒性损伤等诱导肝细胞丧失时处于静息高度分化状态的肝细胞开始分裂增殖，再生反应被精确而仔细的编排和高度调节，肝脏再生调节在多种细胞因子及其它因素协同作用调控下完成。其中HGF、EGF、TGF、TNF和IL等在肝脏再生过程的启动和终止中具有重要的生物学作用。     

肝脏再生

复习肝脏再生的启动、生理过程、网络调控和环境干扰的影响等。     

肝脏再生

进一步研究肝再生，提高对人体病理和生理学的认识，对于肝脏外科的发展，指导肝脏切除和肝移植术后的治疗，以及处理肝功能衰竭等方面都具有重要意义。     

肝脏再生：文献综述

进一步研究肝再生，提高对人体病理和生理学的认识，对于肝脏外科的发展，指导脏脏切除和肝移植术后的治疗，以及处理肝功能衰竭等方面都具有重要意义。     

肝脏再生的奥秘（编译）

部分肝脏切除是刺激肝脏再生的最大因素，体外及大鼠模型的研究表明，许多细胞因子和生长因子与肝脏再生有关，其相互间作用尚不明确，但在不同的再生阶段不同因素间可能有一个瀑布效应。更深入的体外研究应能更多地了解肝脏再生过程，可以有助于更好地选择病人作部分肝脏切除术，也可能提供以有效的治疗方法，救治肝脏再生已经或即将失败的病人。     

肝脏再生(文献综述)

复习肝脏再生的启动、生理过程、网络调控和环境干扰的影响等     

肝部分切除术后肝脏再生调控的研究进展

肝部分切除术(PH)后肝脏能迅速表现出巨大的再生能力.关于肝再生能力的研究一直是肝脏外科领域的热点.现已发现肝脏再生是一个涉及多种效应细胞增殖反应的高度协调的过程,其调控机制非常复杂.笔者就肝部分切除术后其再生调控的研究进展作一简要综述.     

激素与肝脏再生

目的 探讨激素与肝再生的关系。方法 收集和复习近年的有关文献。结果 激素与肝再生的关系十分密切，参与肝再生的过程，起促进或抑制肝再生的作用。结论 激素是调节肝再生的重要因素之一。     

肝脏再生的奥秘(编译)

部分肝脏切除是刺激肝脏再生的最大因素 ,体外及大鼠模型的研究表明 ,许多细胞因子和生长因子与肝脏再生有关 ,其相互间作用尚不明确 ,但在不同的再生阶段不同因素间可能有一个瀑布效应。更深入的体外研究应能更多地了解肝脏再生过程 ,可以有助于更好地选择病人作部分肝脏切除术 ,也可能提供以有效的治疗方法 ,救治肝脏再生已经或即将失败的病人     

肝再生相关分子的研究进展

肝细胞再生的调控是一个复杂的病理生理过程,伴随有大量细胞因子的参与,如早期阶段IL-6、TNF-α,增生阶段HGF、TGFa以及终止阶段TGFβ1等.这些因子相互协调,有序的调节肝细胞的增生.研究肝脏再生分子调控机制对肝切除和肝移植提高肝脏的再生能力具有重要的意义.本文就肝部分切除术后肝细胞再生的相关分子及其作用进行综述.     

肝再生增强因子在隐睾生精细胞中的表达及意义

目的:探讨肝再生增强因子(ALR)在隐睾生精细胞中的表达及其意义。方法:建立SD大鼠隐睾模型(n=20),设立正常(n=10)和手术对照(n=10)。分别采用免疫组化法、免疫荧光法检测术后10、40d(即PND30和PND60)大鼠睾丸组织生精细胞ALR和细胞色素C氧化酶亚单位Ⅱ(COXⅡ)表达情况;Perls染色法检测睾丸中三价铁含量。结果:正常和手术对照组精原细胞ALR呈强表达,隐睾组精原细胞ALR表达显著减弱;同年龄段各组间两两比较,COXⅡ表达水平差异无显著性;术后10d(PND30)隐睾组三价铁含量较同年龄段正常对照组和手术对照组显著减少(P<0.05)。结论:ALR在生精细胞发育的早期起着重要作用,隐睾ALR缺陷所引起的代谢障碍可能是其精子发生障碍的重要机制之一。     

Liver Regeneration in 120 Consecutive Living-Related Liver Donors

Background

Living-related liver transplantation for pediatric patients has become an acceptable, low-risk treatment option. The aim of this study was to assess the extent of donor liver regeneration.

Materials and Methods

Between October 1999 and January 2008, 120 living-related donors provided 109 grafts consisting of segments II and III and 11 grafts consisting of segments II, III, and IV. Volumetric assessment of the donor liver and selected segments was performed using computed tomography. After procurement every graft was weighed. At 7 and 30 days, as well as 12 months after the operation the donor liver remnant was evaluated for differences in volume.

Results

A significant correlation was observed between the liver graft mass and its volume as assessed by computed tomography (r = 0.781; P < .05). Twelve months after procurement, the average regeneration index was significantly higher among donors of segments II, III, and IV (144 ± 23%) versus donors of segments II and III (114 ± 15%; P < .05).

Conclusion

Liver regeneration after procurement of selected liver segments from living donors is a consistent finding. Computed tomography is an accurate imaging modality to track changes in liver volume. This study showed a positive correlation between the size of the liver graft and the regeneration of the liver remnant in the donor.     

Liver Regeneration and Splenic Enlargement in Donors after Living-Donor Liver Transplantation

Liver regeneration after donor hepactectomy offers a unique insight into the process of liver regeneration in normal livers. As the liver restores itself, concurrent splenic enlargement occurs. There are many theories about why this phenomenon takes place: some investigators have proposed a relative portal hypertension that leads to splenic congestion or, perhaps, the presence of a common growth factor that induces both the liver and spleen to enlarge. Between the months of June 2001 and May 2004, 112 live donor liver transplants (LDLTs) were performed in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The total number of donor hepatectomies performed during this period was 113, however, because one of the cases required dual donors. Of our 113 donors, we eventually analyzed the data of 109; 4 patients were lost to follow-up 6 months later and were excluded from our study. The average age of our donor population was 32.32 ± 8.48 years. The mean liver volume at donation was noted to be 1207.72 ± 219.95 cm³, and 6 months later, it was 1027.18 ± 202.41 cm³. Expressed as a percentage of the original volume, the mean liver volume 6 months after hepatectomy was 90.70% ± 12.47% in this series. For right graft donors, mean liver volume after 6 months was 89.68% ± 12.37% of the original liver volume, whereas that for left graft donors was 91.99% ± 12.6%. Only 26 of the 109 (23.85%) donors were able to achieve full regeneration 6 months post-donation. Notably, liver function profiles of all donors were normal when measured 6 months after operation. The average splenic volume at donation as measured by computed tomography (CT) volumetry was 159 ± 58 cm³, and the splenic volume 6 months post-donation was 213 ± 85 cm³. There was a mean increment in splenic volume of 35% ± 28% 6 months after donation. The blood profiles of the donors were monitored; particular attention was given to platelet levels and liver function tests, and these were found to be within normal limits 6 months after operation. Of note, splenic enlargement was significantly greater among right-sided donors than their left-sided counterparts. Greater splenic enlargement was also observed in those donors who achieved full liver regeneration at their evaluation 6 months postoperatively than in those who did not. Although original liver volume was not re-established in most patients 6 months after liver donation, there seemed to have been no untoward effects to the donor. The factors that affect liver regeneration are complex and myriad. Although there is splenic enlargement at 6 months post-donation in donors of LDLT, there are no untoward effects of this enlargement.     

大鼠肝移植后肝再生的实验研究

目的：探讨部分肝移植术后移植肝的再生问题。方法：建立大鼠部分肝移植模型，实验分为肝切除组（PLR组）、全肝移植组（OLT组）和部分肝移植组（POLT组）3组，分别于术后不同时间段取外周血检测总胆红素和谷丙转氨酶水平；取肝组织行组织学检查及流式细胞仪检测移植肝的增殖活性。结果：移植术后1w，肝功能酶学指标增高，后逐步降低；组织学检查术后可见单核细胞浸润，特别在门静脉周围汇管区，肝实质可见点状坏死。术后1个月可见胆管增殖；PLR组和POLT组还可见二倍体和多倍体的肝细胞，中央小静脉、肝窦和叶间静脉轻度扩张。PLR组和POLT组肝细胞增生活跃，3组分别于术后1d、2d、4d达到增殖高峰。结论：部分移植肝和肝切除后肝脏具有同样的增殖活性，但增殖高峰POLT组及OLT组均要晚于肝切除后的肝脏，但移植组增殖周期长。这可能是由于手术操作及肝脏缺血再灌注损伤所致。而持续时间长可能与受体免疫系统产生的细胞因子和激素的调控相关。     

Liver Graft Regeneration in Right Lobe Adult Living Donor Liver Transplantation

Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight-to-recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty-five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 ± 12.6% (range, 58–151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.     

Changes in Splenic Volume during Liver Regeneration

Little is known about the relation between liver regeneration and splenic size. We monitored serial changes in liver and spleen volumes using computed tomography in 24 patients with biliary cancer who underwent right hepatectomy or more extensive liver resection following portal vein embolization (PVE). Nonembolized hepatic segments increased in volume from 316 ± 97 cm³ (34% ± 8% of total liver volume) before PVE to 410 ± 115 cm³ (44% ± 8%) after PVE. The volume of nonembolized hepatic segments (i.e., remnant liver) increased to 617 ± 111 cm³ (59% ± 10% of total liver volume before PVE) 14 days after hepatectomy and then increased slowly to reach 795 ± 231 cm³ (76% ± 16%) 1 year after hepatectomy. Splenic volume increased from 87 ± 29 cm³ before PVE to 104 ± 38 cm³ (119% ± 17% of original volume) after PVE. Splenic volume increased to 137 ± 65 cm³ (155% ± 40%) by 14 days after hepatectomy and to 155 ± 67 cm³ (179% ± 41%) by 28 days after hepatectomy, with no further change at 1 year after hepatectomy (153 ± 92 cm³; 174% ± 79%). The rate of increase in splenic volume within the first 14 days after hepatectomy was 2.7 ± 3.6 cm³/day, correlating well with increases in remnant liver volume (r = 0.64, p = 0.0006). These data indicate that the spleen is enlarged during liver regeneration, suggesting that the liver and spleen share certain common growth regulatory mechanisms.     

Imatinib Mesylate Improves Liver Regeneration and Attenuates Liver Fibrogenesis in CCL4-Treated Mice

Backgrounds  

Imatinib mesylate (STI-571), a tyrosine kinase inhibitor, has previously been demonstrated to attenuate liver fibrogenesis through inhibition of the activation of hepatic stellate cells (HSCs) in CCL₄-treated rat models.     

Regeneration Rate of Left Liver Grafts in Adult Living Donor Liver Transplant

Objective

Appropriate graft weight is important in liver transplant to provide better graft regeneration and to avoid small-for-size syndrome with graft failure. Generally, to protect the donor, the left liver is always selected as the graft. The aim of this study is to evaluate the regeneration rate of the left lobe liver graft in adult living donor liver transplantation (ALDLT).

Patients and Methods

The records and preoperative and postoperative images within 6 months after liver transplantation were reviewed for 9 left and 145 right liver grafts ALDLT enrolled in this study. We calculated the graft volume at 6 months after transplantation divided by the standard liver volume as the regeneration ratio. The regeneration rate of the group with a left liver graft ALDLT was compared with our right liver graft group.

Results

The liver graft regeneration ratio of the left lobe was 85.3 ± 11.0 (range, 61-97), slightly lower than the right liver graft (91.2 ± 12.6%; range, 58-151). In the graft-recipient body weight ratio (GRWR) > 1, the regenerative rate was slightly higher than the group of GRWR < 1. The regeneration ratio was proportional to spleen volume and portal inflow (P = .039).

Conclusion

Either the right or left liver graft can achieve sufficient regeneration in ALDLT. However, there was a slightly lower regeneration rate among the left liver graft and GRWR < 1 groups. Spleen size, a major factor contributing to portal inflow, may directly trigger graft regeneration after transplantation with a linear correlation in growth.