Tumor necrosis factor-α mediates JNK activation response to intestinal ischemia-reperfusion injury
Tumor necrosis factor-α mediates JNK activation response to intestinal ischemia-reperfusion injury
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DOI：
10.3748/wjg.v19.i30.4925
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发表时间：
2013-08-14
影响因子：
4.3
通讯作者：
Wu, Bin
中科院分区：
文献类型：
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作者：
Yang, Qi;Zheng, Feng-Ping;Wu, Bin
目的：探讨肿瘤坏死因子-α (TNF-α) 是否通过 c-Jun N 末端激酶 (JNK) 激活介导缺血再灌注 (I/R) 诱导的肠粘膜损伤。 方法：在本研究中，通过闭塞大鼠肠系膜上动脉 60 分钟，然后闭塞 60 分钟来诱导肠 I/R。 再灌注，并用 TNF-α 抑制剂、己酮可可碱或 TNF-α 抗体英夫利昔单抗对大鼠进行预处理。手术后，收集部分肠道用于组织学分析。收集粘膜层用于提取 RNA 和蛋白质，用于进一步的实时聚合酶链反应、酶联免疫吸附测定和蛋白质印迹分析。分析TNF-α表达、肠粘膜损伤、细胞凋亡、凋亡蛋白激活和JNK信号通路。结果：I/R显着增强粘膜TNF-α在mRNA和蛋白水平的表达，诱导严重粘膜损伤和细胞凋亡，激活caspase-9/caspase-3，激活JNK信号通路 途径。己酮可可碱预处理显着下调 TNF-α mRNA 和蛋白质水平，而英夫利昔单抗预处理不影响 I/R 诱导的 TNF-α 表达。然而，己酮可可碱或英夫利昔单抗预处理可显着抑制缺血再灌注引起的粘膜损伤和细胞凋亡，并显着抑制 caspase-9/3 和 JNK 信号传导的激活。 结论：结果表明，肠道缺血再灌注损伤存在 TNF-α 介导的 JNK 激活反应。 (c)2013年百事登。版权所有。
AIM: To investigate whether tumor necrosis factor-alpha (TNF-alpha) mediates ischemia-reperfusion (I/R)-induced intestinal mucosal injury through c-Jun N-terminal kinase (JNK) activation.METHODS: In this study, intestinal I/R was induced by 60-min occlusion of the superior mesenteric artery in rats followed by 60-min reperfusion, and the rats were pretreated with a TNF-alpha inhibitor, pentoxifylline, or the TNF-alpha antibody infliximab. After surgery, part of the intestine was collected for histological analysis. The mucosal layer was harvested for RNA and protein extraction, which were used for further real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blotting analyses. The TNF-alpha expression, intestinal mucosal injury, cell apoptosis, activation of apoptotic protein and JNK signaling pathway were analyzed.RESULTS: I/R significantly enhanced expression of mucosal TNF-alpha at both the mRNA and protein levels, induced severe mucosal injury and cell apoptosis, activated caspase-9/caspase-3, and activated the JNK signaling pathway. Pretreatment with pentoxifylline markedly downregulated TNF-alpha at both the mRNA and protein levels, whereas infliximab pretreatment did not affect the expression of TNF-alpha induced by I/R. However, pretreatment with pentoxifylline or infliximab dramatically suppressed I/R-induced mucosal injury and cell apoptosis and significantly inhibited the activation of caspase-9/3 and JNK signaling.CONCLUSION: The results indicate there was a TNF-alpha-mediated JNK activation response to intestinal I/R injury. (c) 2013 Baishideng. All rights reserved.