缺血再灌注对大鼠肝脏再生的影响。

Effects of ischaemia and reperfusion on liver regeneration in rats.

作者信息

Foschi D, Castoldi L, Lesma A, Musazzi M, Benevento A, Trabucchi E

机构信息

First Department of Surgery and Surgical Therapeutics, Ospedale Maggiore, University of Milan, Italy.

出版信息

Eur J Surg. 1993 Aug;159(8):393-8.

PMID:8218549

Abstract

OBJECTIVE

To assess the effects of oxygen free radicals on liver regeneration in rats after 80% hepatectomy.

DESIGN

Open laboratory study.

SETTING

Institute of Biomedical Sciences, University of Milan, Italy.

MATERIAL

Female Sprague-Dawley rats.

INTERVENTIONS

After laparotomy 122 rats had ischaemia induced by clamping of the portal vein and hepatic artery, and 93 rats had manipulation of the vessels only. They were then allowed to recover before 80% hepatectomy was done. Absolute controls (n = 16) did not have a laparotomy. Mortality was recorded, and surviving rats were killed one, three, five, and seven days after operation. A further 10 rats had 80% hepatectomies and then underwent a 10 minute period of ischaemia 24 hours later. These animals were killed after three days. In yet more experiments 38 rats underwent 80% hepatectomies and were then divided into four groups: 8 were given allopurinol 50 mg/kg/day starting three days before operation; 8 were given superoxide dismutase 4.16 mg/kg intraperitoneally 30 minutes before induction of ischaemia; 12 were given verapamil 0.1 mg/kg 30 minutes before induction of ischaemia; and 10 were given saline (controls).

MAIN OUTCOME MEASURES

Incorporation of tritiated thymidine into DNA, differences in liver weights, and lipid peroxide concentrations.

RESULTS

43 rats died after ischaemia/reperfusion and 19 after hepatectomy alone. Ischaemia/reperfusion caused a significant reduction in the incorporation of tritiated thymidine into DNA 24 hours after hepatectomy (p < 0.01), and significant inhibition of recovery of liver weight three (p < 0.01) and five (p < 0.05) days after hepatectomy. These effects were associated with high lipid peroxide concentrations at three days. Allopurinol (p < 0.01, p < 0.05), superoxide dismutase (p < 0.01, p < 0.01) and verapamil (p < 0.01, N.S.) reduced the effects of ischaemia/reperfusion on liver weights or lipid peroxide concentrations three days after hepatectomy.

CONCLUSION

A 10 minute period of ischaemia followed by reperfusion temporarily reduces liver regeneration after 80% hepatectomy in rats.

摘要

目的

评估氧自由基对80%肝切除术后大鼠肝脏再生的影响。

设计

开放性实验室研究。

地点

意大利米兰大学基础生物医学科学研究所。

材料

雌性斯普拉格-道利大鼠。

干预措施

剖腹术后，122只大鼠通过钳夹门静脉和肝动脉诱导缺血，93只大鼠仅进行血管操作。然后让它们恢复，再进行80%肝切除术。绝对对照组（n = 16）未进行剖腹手术。记录死亡率，存活大鼠在术后1天、3天、5天和7天处死。另外10只大鼠进行80%肝切除，然后在24小时后经历10分钟缺血。这些动物在3天后处死。在更多实验中，38只大鼠进行80%肝切除，然后分为四组：8只在术前3天开始给予别嘌呤醇50 mg/kg/天；8只在缺血诱导前30分钟腹腔注射超氧化物歧化酶4.16 mg/kg；12只在缺血诱导前30分钟给予维拉帕米0.1 mg/kg；10只给予生理盐水（对照组）。

主要观察指标

氚标记胸腺嘧啶核苷掺入DNA的情况、肝脏重量差异和脂质过氧化物浓度。

结果

43只大鼠在缺血/再灌注后死亡，19只在单纯肝切除后死亡。缺血/再灌注导致肝切除术后24小时氚标记胸腺嘧啶核苷掺入DNA显著减少（p < 0.01），并在肝切除术后3天（p < 0.01）和5天（p < 0.05）显著抑制肝脏重量恢复。这些效应与术后3天脂质过氧化物浓度升高有关。别嘌呤醇（p < 0.01，p < 0.05）、超氧化物歧化酶（p < 0.01，p < 0.01）和维拉帕米（p < 0.立，无显著性差异）在肝切除术后3天减轻了缺血/再灌注对肝脏重量或脂质过氧化物浓度的影响。