P38 MAPK Pharmacological Inhibitor SB203580 Alleviates Total Parenteral Nutrition-Induced Loss of Intestinal Barrier Function but Promotes Hepatocyte Lipoapoptosis
P38 MAPK Pharmacological Inhibitor SB203580 Alleviates Total Parenteral Nutrition-Induced Loss of Intestinal Barrier Function but Promotes Hepatocyte Lipoapoptosis
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P38 MAPK 药理抑制剂 SB203580 减轻全肠外营养引起的肠屏障功能丧失，但促进肝细胞脂肪凋亡
DOI：
10.1159/000457933
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Cai, Wei
中科院分区：
文献类型：
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作者：
Xiao, Yong-Tao;Yan, Wei-Hui;Cai, Wei
背景与目的：我们之前的研究提供了证据表明p38丝裂原激活蛋白激酶（MAPK）参与全肠外营养（TPN）相关并发症，但其确切作用和机制尚未完全了解。本研究旨在评估 p38 MAPK 抑制剂 SB203580 在 TPN 诱导的肠道屏障功能丧失和肝脏疾病中的作用。方法：使用 TPN 啮齿动物模型分析 SB203580 在 TPN 相关并发症中的作用。通过跨上皮电阻 (TER) 和 Caco-2 细胞的细胞旁通透性评估肠屏障功能。棕榈酸（PA）用于体外诱导肝脂肪细胞凋亡。使用Caspase-3/7和脂质染色检测脂肪凋亡。结果：在本研究中，我们表明 SB203580 治疗显着抑制大鼠 TPN 介导的肠道通透性。 SB203580 治疗通过抑制 p38/ATF-2 信号传导，显着抑制 IL-1 β 诱导的 Caco-2 细胞紧密连接通透性增加。出乎意料的是，SB203580 治疗增强了 TPN 模型中的肝脏脂肪凋亡。 SB203580 治疗显着增强了棕榈酸 (PA) 诱导的人肝细胞肝脂肪凋亡。结论：我们证明 p38 MAPK 抑制剂 SB203508 在 TPN 模型中改善肠道屏障功能，但促进肝脏脂肪凋亡。 (C) 2017 作者由 S. Karger AG 出版，巴塞尔
Background & Aims: Our previous studies have provided evidence that p38 mitogenactivated protein kinase (MAPK) is involved in total parenteral nutrition (TPN)-associated complications, but its exact effects and mechanisms have not been fully understood. This study aimed to evaluate the roles of p38 MAPK inhibitor SB203580 in the TPN-induced loss of intestinal barrier function and liver disease. Methods: A rodent model of TPN was used to analyze the roles of SB203580 in TPN-associated complications. Intestinal barrier function was evaluated by transepithelial electrical resistance (TER) and paracellular permeability in Caco-2 cells. The palmitic acid (PA) was used to induce hepatic lipoapoptosis in vitro. The lipoapoptosis was detected using Caspase-3/7 and lipid staining. Results: In the present study, we showed that SB203580 treatment significantly suppressed TPN-mediated intestinal permeability in rats. SB203580 treatment significantly inhibited IL-1 beta-induced an increase in tight junction permeability of Caco-2 cells via repressing the p38/ATF-2 signaling. Unexpectedly, SB203580 treatment enhanced hepatic lipoapoptosis in the model of TPN. Palmitic acid (PA)-induced hepatic lipoapoptosis in human liver cells was significantly augmented by the SB203580 treatment. Conclusions: We demonstrate that the p38 MAPK inhibitor SB203508 ameliorates intestinal barrier function but promotes hepatic lipoapoptosis in model of TPN. (C) 2017 The Author(s) Published by S. Karger AG, Basel