Galectin-1 attenuates hepatic ischemia reperfusion injury in mice
Galectin-1 attenuates hepatic ischemia reperfusion injury in mice
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Galectin-1 可减轻小鼠肝脏缺血再灌注损伤。
DOI：
10.1016/j.intimp.2019.105997
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Zheng S.
中科院分区：
文献类型：
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作者：
Ye Y;Wang W;Zhang W;Peng Y;Liu Y;Yu S;Chen Q;Geng L;Zhou L;Xie H;Lai M;Yu J;Zheng S.
背景肝缺血再灌注损伤（IRI）是肝切除手术和移植过程中发生器官功能障碍的主要原因。 Galectin-1 是一种在淋巴器官上表达的内源性凝集素，在控制先天性和适应性免疫中发挥着重要作用。本研究旨在确定半乳糖凝集素-1 (galectin-1) 在肝脏 IRI 中的治疗作用及其潜在机制。方法对雄性 C57BL/6 小鼠进行 90 分钟的部分肝缺血，然后再灌注，用或不用重组半乳糖凝集素-1 (rGal-1) 或中和抗 IL-10 抗体治疗。再灌注后6小时和24小时处死小鼠。通过 qPCR 和 ELISA 测定肝损伤相关酶并测量细胞因子/趋化因子。结果与对照组相比，给予 rGal-1 显着减弱肝脏 IRI，包括血清 ALT/AST 水平显着降低和肝脏组织学评分改善。与对照组相比，rGal-1 治疗可减少 TUNEL 阳性凋亡肝细胞，减弱促炎细胞因子（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 IL-10 表达。此外，rGal-1 在体内和体外增加肝巨噬细胞中 IL-10 的产生。使用中和性抗IL-10抗体阻断IL-10可逆转galectin-1对小鼠肝脏IRI的保护作用。结论这些数据表明galectin-1可能通过IL-10依赖性机制减弱肝脏IRI，这是一个有前途的治疗靶点。
BackgroundHepatic 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.MethodsMale 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.ResultsAdministration 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 macrophagesin vivoandin vitro. Blockade of IL-10 using neutralizing anti-IL-10 antibody reversed the protection of galectin-1 in hepatic IRI in mice.ConclusionThese data suggest that galectin-1 may attenuate hepatic IRI via an IL-10-dependent mechanism, which is a promising therapeutic target.