Emodin Protects Against Concanavalin A-Induced Hepatitis in Mice Through Inhibiting Activation of the p38 MAPK-NF-κB Signaling Pathway
Emodin Protects Against Concanavalin A-Induced Hepatitis in Mice Through Inhibiting Activation of the p38 MAPK-NF-κB Signaling Pathway
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DOI：
10.1159/000373971
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Chen, Zhi
中科院分区：
文献类型：
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作者：
Xue, Jihua;Chen, Feng;Chen, Zhi
目的：研究大黄素对刀豆蛋白A(ConA)诱导的小鼠肝炎的影响，并探讨其分子机制。方法：Balb/c雄性小鼠静脉注射ConA(20 mg/kg)，建立暴发型肝炎模型。分别在ConA注射前后灌胃给予大黄素。检测小鼠肝脏、RAW264.7和EL4细胞的促炎细胞因子和趋化因子水平、肝组织中CD4(+)和F4/80(+)细胞的数量以及p38MAPK和核因子-kappaB的磷酸化水平。结果：大黄素可显著降低血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平，减轻肝组织坏死，对T细胞介导性肝炎有明显的保护作用。此外，大黄素可显著降低肝内促炎细胞因子和趋化因子的表达，包括肿瘤坏死因子(INF)-α、干扰素(IFN)-γ、白介素1(IL)-1β、IL-6、IL-12、诱导型一氧化氮合酶(INOS)、整合素αM(ITGAM)、趋化因子(C-C基序)配体2(CCL2)、巨噬细胞炎性蛋白2(MIP-2)和趋化因子受体2(CXCR2)。此外，大黄素可显著抑制ConA处理的小鼠肝脏、RAW264.7和EL4细胞中CD4(+)和F4/80(+)细胞的数量以及p38MAPK和NF-kappaB的活化。结论：大黄素对ConA诱导的小鼠肝损伤有一定的保护作用，其机制可能与抑制CD4(+)和F4/80(+)细胞的浸润及激活CD4(+)T细胞和巨噬细胞的p38MAPK-NF-kappa B通路有关。版权所有(C)2015年S.Karger AG，巴塞尔
Background/Aims: To investigate the effects of emodin on concanavalin A (Con A)-induced hepatitis in mice and to elucidate its underlying molecular mechanisms. Methods: A fulminant hepatitis model was established successfully by the intravenous administration of Con A (20 mg/kg) to male Balb/c mice. Emodin was administered to the mice by gavage before and after Con A injection. The levels of pro-inflammatory cytokines and chemokines, numbers of CD4(+) and F4/80(+) cells infiltrated into the liver, and amounts of phosphorylated p38 MAPK and NF-kappa B in mouse livers and RAW264.7 and EL4 cells were measured. Results: Pretreatment with emodin significantly protected the animals from T cell-mediated hepatitis, as shown by the decreased elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as reduced hepatic necrosis. In addition, emodin pretreatment markedly reduced the intrahepatic expression of pro-inflammatory cytokines and chemokines, including tumor necrosis factor (INF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1 beta, IL-6, IL-12, inducible nitric oxide synthase (iNOS), integrin alpha M (ITGAM), chemokine (C-C motif) ligand 2 (CCL2), macrophage inflammatory protein 2 (MIP-2) and chemokine (CXC motif) receptor 2 (CXCR2). Furthermore, emodin pretreatment dramatically suppressed the numbers of CD4(+) and F4/80(+) cells infiltrating into the liver as well as the activation of p38 MAPK and NF-kappa B in Con A-treated mouse livers and RAW264.7 and EL4 cells. Conclusion: The results indicate that emodin pretreatment protects against Con A-induced liver injury in mice; these beneficial effects may occur partially through inhibition of both the infiltration of CD4(+) and F4/80(+) cells and the activation of the p38 MAPK-NF-kappa B pathway in CD4(+) T cells and macrophages. Copyright (C) 2015 S. Karger AG, Basel