库普弗细胞失活对大鼠部分肝移植后移植物存活及肝再生的影响。

Effects of Kupffer cell inactivation on graft survival and liver regeneration after partial liver transplantation in rats.

作者信息

Luo Hang-Yu, Ma Shan-Fang, Qu Ji-Fu, Tian De-Hu

机构信息

Department of Emergency Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2015 Feb;14(1):56-62. doi: 10.1016/s1499-3872(14)60291-5.

DOI:10.1016/s1499-3872(14)60291-5

PMID:25655291

Abstract

BACKGROUND

Gadolinium chloride (GdCl3) selectively inactivates Kupffer cells and protects against ischemia/reperfusion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplantation (PLTx) is not clear. This study was to investigate the role of GdCl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process.

METHODS

PLTx (30% partial liver transplantation) was performed using Kamada's cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose (5 mg/kg) and high-dose (10 mg/kg) GdCl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regeneration by PCNA staining and BrdU uptake, apoptosis by TUNEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting.

RESULTS

GdCl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine aminotransferase and aspartate aminotransferase (P>0.05). GdCl3 pretreatment induced apoptosis and inhibited IL-6 overexpression and STAT3 phosphorylation after PLTx in graft tissues.

CONCLUSION

Kupffer cells may contribute to the liver regeneration after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway.

摘要

背景

氯化钆（GdCl3）可选择性地使库普弗细胞失活，并预防缺血/再灌注损伤和内毒素损伤。然而，库普弗细胞失活对部分肝移植（PLTx）后肝脏再生的影响尚不清楚。本研究旨在探讨GdCl3预处理在PLTx后移植物功能中的作用，并探索这一过程中涉及的潜在机制。

方法

采用Kamada袖套技术进行PLTx（30%部分肝移植），不进行肝动脉重建。大鼠随机分为对照低剂量（5mg/kg）和高剂量（10mg/kg）GdCl3组。通过丙氨酸氨基转移酶和天冬氨酸氨基转移酶的血浆水平测定肝损伤，通过PCNA染色和BrdU摄取测定肝脏再生，通过TUNEL法测定细胞凋亡。通过ELISA和蛋白质印迹法测量IL-6和p-STAT3水平。