半乳糖凝集素-1 减轻小鼠肝缺血再灌注损伤。

Galectin-1 attenuates hepatic ischemia reperfusion injury in mice.

机构信息

Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.

出版信息

Int Immunopharmacol. 2019 Dec;77:105997. doi: 10.1016/j.intimp.2019.105997. Epub 2019 Nov 21.

DOI:10.1016/j.intimp.2019.105997

PMID:31761683

Abstract

BACKGROUND

Hepatic ischemia reperfusion injury (IRI) is a primary cause of organ dysfunction occurring during liver resection surgery and transplantation. Galectin-1, an endogenous lectin expressed on lymphoid organs, plays an important role in governing innate and adaptive immunity. This study was designed to determine the therapeutic role of galectin-1 and underlying mechanism in hepatic IRI.

METHODS

Male C57BL/6 mice were subjected to 90 min of partial hepatic ischemia followed by reperfusion with or without treatment with recombinant galectin-1 (rGal-1) or neutralizing anti-IL-10 antibody. Mice were sacrificed at 6 and 24 h following reperfusion. Liver damage related enzymes were determined and cytokines/chemokines were measured by qPCR and ELISA.

RESULTS

Administration of rGal-1 significantly attenuated hepatic IRI, including a remarkable reduction in serum ALT/AST levels and an improved liver histology score compared to controls. rGal-1 treatment reduced TUNEL positive apoptotic hepatocytes, attenuated proinflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12, IFN-γ, IL-17) and chemokines (CXCL-1, CXCL-10) levels, but upregulated IL-10 expression, compared with controls. In addition, rGal-1 increased the production of IL-10 in hepatic macrophages in vivo and in vitro. Blockade of IL-10 using neutralizing anti-IL-10 antibody reversed the protection of galectin-1 in hepatic IRI in mice.

CONCLUSION

These data suggest that galectin-1 may attenuate hepatic IRI via an IL-10-dependent mechanism, which is a promising therapeutic target.

摘要

背景

肝缺血再灌注损伤（IRI）是肝切除术和肝移植过程中器官功能障碍的主要原因。半乳糖凝集素-1（Galectin-1）是一种在淋巴器官表达的内源性凝集素，在调节固有和适应性免疫方面发挥着重要作用。本研究旨在确定 Galectin-1 在肝 IRI 中的治疗作用及其潜在机制。

方法

雄性 C57BL/6 小鼠接受 90 分钟的部分肝缺血，然后再灌注，同时给予重组 Galectin-1（rGal-1）或中和抗 IL-10 抗体治疗。再灌注后 6 和 24 小时处死小鼠。通过 qPCR 和 ELISA 测定肝损伤相关酶和细胞因子/趋化因子。

结果

与对照组相比，rGal-1 给药显著减轻了肝 IRI，包括血清 ALT/AST 水平显著降低和肝组织学评分改善。rGal-1 治疗减少了 TUNEL 阳性凋亡肝细胞，减轻了促炎细胞因子（TNF-α、IL-6、IL-1β、IL-12、IFN-γ、IL-17）和趋化因子（CXCL-1、CXCL-10）水平，但上调了 IL-10 的表达。此外，rGal-1 增加了体内和体外肝巨噬细胞中 IL-10 的产生。使用中和抗 IL-10 抗体阻断 IL-10 逆转了 Galectin-1 在小鼠肝 IRI 中的保护作用。