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在冷缺血/温再灌注损伤模型中,抗凝血酶通过调节肝脏炎症来预防细胞凋亡。

Antithrombin prevents apoptosis by regulating inflammation in the liver in a model of cold ischemia/warm reperfusion injury.

作者信息

Isik Sevil, Tuncyurek Pars, Zengin Neslihan Inci, Demirbag Ali Eba, Atalay Fuat, Yilmaz Sezai, Orug Taner

机构信息

Department of General Surgery, Ordu University, Ordu, Turkey.

出版信息

Hepatogastroenterology. 2012 Mar-Apr;59(114):453-7. doi: 10.5754/hge11317.

DOI:10.5754/hge11317
PMID:21940387
Abstract

BACKGROUND/AIMS: Hepatic ischemia-reperfusion injury is a major problem in liver surgery. To modulate the complex process of inflammation, additional drugs to add to well-defined organ preserving solutions have been sought. The aim of the current study was to investigate the additive potential of antithrombin (AT) in liver preservation.

METHODOLOGY

Female Wistar rats were randomized into four groups: sham (Group I), experiment model (Group II), and treatment groups with AT (250U/kg) administration systematically (Group III) or locally (Group IV) before hepatectomy. UW solution was used for liver preservation for 24h at 4°C. The livers in group II, III and IV were reperfused 1h and histopathological parameters were evaluated microscopically. Apoptosis was assessed with TUNEL test.

RESULTS

Karyorrhexis was lower in the local treatment with AT group. Sinusoidal desquamation and mononuclear cell infiltration was higher in the experimental model group. Sinusoidal enlargement was higher in the systemic AT treatment group and neutrophil infiltration to sinusoids was lowest in the local treatment group. Apoptosis of hepatocytes and sinusoidal cells were significantly suppressed in rats that were treated with AT via portal vein infusion.

CONCLUSIONS

AT treatment obviously contributed to liver preservation in our model; the effects on apoptosis and inflammation were prominent. Therefore, AT should be considered as a potent agent although its clinical role has yet to be defined in ex-vivo hepatic preservation.

摘要

背景/目的:肝缺血再灌注损伤是肝脏手术中的一个主要问题。为了调控炎症的复杂过程,人们一直在寻找可添加到明确的器官保存液中的其他药物。本研究的目的是探讨抗凝血酶(AT)在肝脏保存中的附加作用潜力。

方法

将雌性Wistar大鼠随机分为四组:假手术组(I组)、实验模型组(II组)以及在肝切除术前全身(III组)或局部(IV组)给予AT(250U/kg)的治疗组。采用UW液在4℃下保存肝脏24小时。II、III和IV组的肝脏再灌注1小时,并通过显微镜评估组织病理学参数。采用TUNEL检测评估细胞凋亡情况。

结果

AT局部治疗组的核碎裂较少。实验模型组的窦状隙剥脱和单核细胞浸润较多。全身AT治疗组的窦状隙扩张较多,而局部治疗组窦状隙的中性粒细胞浸润最少。通过门静脉输注AT治疗的大鼠,其肝细胞和窦状隙细胞的凋亡明显受到抑制。

结论

在我们的模型中,AT治疗对肝脏保存有明显作用;对细胞凋亡和炎症的影响显著。因此,尽管AT在体外肝脏保存中的临床作用尚未明确,但应将其视为一种有效的药物。

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