15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy
15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy
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DOI：
10.1016/j.biopha.2016.03.012
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发表时间：
2016-05-01
影响因子：
7.5
通讯作者：
Guo, Chuanyong
中科院分区：
文献类型：
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作者：
Chen, Kan;Li, Jingjing;Guo, Chuanyong
目的：在这项研究中，我们证实了15 d-PGJ 2在刀豆球蛋白A（ConA）诱导的小鼠暴发性hepatitis中的保护作用，并探讨了潜在的mechanism.Materials和方法：Balb/C小鼠用ConA（25 mg/kg）注射诱导急性暴发性hepatitis，和15 d-PGJ 2（2.5-10 μ g）在ConA注射后30 min给药。结果：ConA刺激后，细胞因子肿瘤坏死因子α（TNF-α）和白细胞介素1 β（IL-1 β）的表达上调，细胞凋亡和自噬活性增加，HO-1、Nrf 2、JNK的表达增加，Bcl-2活性增加。用15 d-PGJ 2治疗减轻了ConA诱导的暴发性肝炎的病理效应，并显著降低了注射后TNF-α、IL-1 β和ROS的水平。结论：15 d-PGJ 2通过上调抗氧化应激因子HO-1的表达，减少细胞因子和ROS的产生，从而抑制ROS诱导的肝细胞自噬，减轻ConA诱导的小鼠急性肝损伤。(C)2016 Elsevier Masson SAS。All rights reserved.
Objective: In this study, we confirmed a protective effect of 15d-PGJ2 in concanavalin A (ConA)-induced fulminant hepatitis in mice and investigated the potential mechanism.Materials and methods: Balb/C mice were injected with ConA (25 mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5-10 mu g) was administered 30 min after the ConA injection. The histological grade, pro-inflammatory cytokine and ROS levels, apoptosis and autophagy activity, the expression of HO-1, Nrf2, JNK and Bcl-2 activity were determined 2, 4, and 8 h after the ConA injection.Results: Following ConA challenge, the expression of cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) was up-regulated. Treatment with 15d-PGJ2 reduced the pathological effects of ConA-induced fulminant hepatitis and significantly reduced the levels of TNF-alpha, IL-1 beta and ROS after injection. 15d-PGJ2 inhibited apoptosis and autophagic cell death, facilitated Nrf2 nuclear translocation, increased HO-1 expression and suppressed the JNK activation.Conclusion: 15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating the anti-oxidative stress factor HO-1 and reducing the production of cytokines and ROS, thereby inhibiting hepatic cell autophagy probably induced by ROS. (C) 2016 Elsevier Masson SAS. All rights reserved.