生物人工肝减轻肝大部切除术后肠黏膜损伤和肠道屏障功能障碍：在猪模型中的研究。

Bioartificial liver attenuates intestinal mucosa injury and gut barrier dysfunction after major hepatectomy: Study in a porcine model.

作者信息

Nastos Constantinos, Kalimeris Konstantinos, Papoutsidakis Nikolaos, Defterevos George, Pafiti Agathi, Kalogeropoulou Eleni, Zerva Loukia, Nomikos Tzortzis, Papalois Apostolos, Kostopanagiotou Georgia, Smyrniotis Vasillios, Arkadopoulos Nikolaos

机构信息

Second Department of Surgery, School of Medicine, National and Kapodistrian University of Athens, Aretaieion University Hospital, Athens, Greece.

Second Department of Anesthesiology, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.

出版信息

Surgery. 2016 Jun;159(6):1501-1510. doi: 10.1016/j.surg.2015.12.018. Epub 2016 Feb 2.

DOI:10.1016/j.surg.2015.12.018

PMID:26847802

Abstract

BACKGROUND

The aim of this study was to evaluate whether bioartificial liver support can attenuate gut mucosa injury in a porcine model of posthepatectomy liver dysfunction.

METHODS

Posthepatectomy liver failure was induced in pigs combining major (70%) liver resection and ischemia/reperfusion injury. An ischemic period of 150 minutes was followed by reperfusion for 24 hours. Animals were divided randomly into 2 groups: a control group (n = 6) that received standard critical care and a bioartificial liver support group (Hepat, n = 6) that were subjected to extracorporeal liver support for 6 hours during reperfusion. Intestinal mucosal injury, bacterial translocation, and endotoxin translocation were evaluated in all animals. Intestinal mucosa was also evaluated with markers of oxidative injury and immunohistochemical staining for caspase 3.

RESULTS

When compared with median values, the control group, animals in the Hepat group had a lesser intestinal mucosal injury score (4.0 [range:2.0-5.0] vs 1.0 [range:1.0-2.0]; P < .01), decreased bacterial translocation in the portal and the systemic circulation at 24 hours of reperfusion (P < .05), and decreased portal and systemic endotoxin levels at 24 hours (P < .05). At 24 hours after reperfusion, mucosal protein carbonyls and malondialdehyde levels were decreased in Hepat animals (0.57 nmol/mg [range:0.32-0.70] vs 0.33 nmol/mg [range:0.03-0.53] and 3.85 nmol/mg [range:3.01-6.43] vs 3.27 nmol/mg [range:1.46-3.55], respectively; P < .05). There was no difference in tissue caspase staining.

CONCLUSION

Bioartificial liver support seems to attenuate intestinal mucosal injury and gut barrier dysfunction after major hepatectomy.

摘要

背景

本研究旨在评估生物人工肝支持能否减轻肝切除术后肝功能不全猪模型的肠黏膜损伤。

方法

通过联合70%的大肝切除和缺血/再灌注损伤诱导猪发生肝切除术后肝衰竭。缺血150分钟后再灌注24小时。动物被随机分为两组：接受标准重症监护的对照组（n = 6）和在再灌注期间接受6小时体外肝支持的生物人工肝支持组（Hepat组，n = 6）。评估所有动物的肠黏膜损伤、细菌移位和内毒素移位。还通过氧化损伤标志物和半胱天冬酶3免疫组化染色评估肠黏膜。

结果

与中位数相比，Hepat组动物的肠黏膜损伤评分低于对照组（4.0[范围：2.0 - 5.0]对1.0[范围：1.0 - 2.0]；P <.01），再灌注24小时时门静脉和体循环中的细菌移位减少（P <.05），24小时时门静脉和全身内毒素水平降低（P <.05）。再灌注24小时后，Hepat组动物的黏膜蛋白羰基和丙二醛水平降低（分别为0.57 nmol/mg[范围：0.32 - 0.70]对0.33 nmol/mg[范围：0.03 - 0.53]和3.85 nmol/mg[范围：3.01 - 6.43]对3.27 nmol/mg[范围：1.46 - 3.55]；P <.05）。组织半胱天冬酶染色无差异。