特利加压素与脾切除术对大鼠部分肝切除术后肝再生影响的对比研究。

Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats.

机构信息

Department of General, Visceral and Transplantation Surgery, RWTH Aachen University Hospital, Aachen, Germany.

Department of Urology, Helios Hospital, Berlin-Buch, Germany.

出版信息

Hepatobiliary Pancreat Dis Int. 2017 Oct 15;16(5):506-511. doi: 10.1016/S1499-3872(17)60036-5.

DOI:10.1016/S1499-3872(17)60036-5

PMID:28992883

Abstract

BACKGROUND

Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70% partial hepatectomy.

METHODS

Seventy-two male Wistar rats were randomly assigned into three groups (n=24 in each group): 70% partial hepatectomy as control (PHC), 70% partial hepatectomy with splenectomy (PHS) or 70% partial hepatectomy with a micropump for terlipressin administration (PHT). Eight rats in each group were sacrificed on postoperative day (POD) 1, 3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine (BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.

RESULTS

The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups (PHT: 8.13±1.55, 10.38±1.30, 6.25±0.89 cmHO and PHS: 7.50±0.93, 8.88±2.42, 5.75±1.04 cmHO) was lower compared to the control group (PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmHO). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1 (BrdU: PHS vs PHC, 20.85%±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96%±11.69%). However, none of the differences were statistically significant.

CONCLUSIONS

Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.

摘要

背景

肝切除术后由于肝残余不足导致的肝功能衰竭是肝外科的一种可怕并发症。人们一直在努力寻找新的策略来支持肝再生。本研究旨在探讨特利加压素与脾切除术对大鼠 70%部分肝切除术后肝功能和肝再生的影响。

方法

72 只雄性 Wistar 大鼠随机分为三组（每组 24 只）：70%部分肝切除术（PHC）作为对照、70%部分肝切除加脾切除术（PHS）或 70%部分肝切除加特利加压素微泵给药（PHT）。每组 8 只大鼠分别于术后第 1、3 和 7 天处死。为了评估肝再生，使用溴脱氧尿苷（BrdU）和 Ki-67 标记对肝组织进行免疫组织化学分析。在术后第 1、3 和 7 天测定门静脉压、血清肌酐、尿素、白蛋白、胆红素和凝血酶原时间以及肝重、体重及其比值。

结果

各组间肝重、体重及其比值无统计学差异。在术后第 1、3 和 7 天，干预组（PHT：8.13±1.55、10.38±1.30、6.25±0.89 cmH2O 和 PHS：7.50±0.93、8.88±2.42、5.75±1.04 cmH2O）的门静脉压低于对照组（PHC：8.63±2.06、10.50±2.45、6.50±2.67 cmH2O）。干预组的肝细胞增殖延迟，尤其是在脾切除术后第 1 天（BrdU：PHS 与 PHC，20.85%±13.05%与 28.11%±10.10%；Ki-67，20.14%±14.10%与 23.96%±11.69%）。然而，这些差异均无统计学意义。