Increased intestinal inflammatory response and gut barrier dysfunction in Nrf2-deficient mice after traumatic brain injury
Increased intestinal inflammatory response and gut barrier dysfunction in Nrf2-deficient mice after traumatic brain injury
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DOI：
10.1016/j.cyto.2008.07.005
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发表时间：
2008-10-01
期刊：
影响因子：
3.8
通讯作者：
Yin, Hongxia
中科院分区：
文献类型：
--
作者：
Jin, Wei;Wang, Handong;Yin, Hongxia
目的：探讨核因子红系2相关因子2(NRF2)在创伤性脑损伤小鼠肠道炎症反应和肠屏障功能障碍中的作用。方法：野生型Nrf2(+/+)和Nrf2(-/-)缺陷小鼠造成中重度落体撞击-加速性颅脑损伤。用凝胶电泳法测定核因子-kappaB，用酶联免疫吸附试验测定肿瘤坏死因子-α、白介素1-β和白介素6，免疫组织化学法测定细胞间黏附分子-1，乳果糖/甘露醇法测定肠通透性(L/M)，显色法测定血浆内毒素。结果：伤后2 4h，Nrf2(-/-)缺陷小鼠肠道组织中NF-kappaB、促炎性细胞因子和ICAM-1的水平显著高于Nrf2(+/+)小鼠。此外，与Nrf2(+/+)小鼠相比，Nrf2(-/-)小鼠的肠道通透性和血浆内毒素水平更高。结论：Nrf2在限制颅脑损伤后肠道炎症反应和肠屏障功能障碍方面具有重要的保护作用。(C)2008爱思唯尔有限公司。保留所有权利。
Aim: To explore the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in traumatic brain injury (TBI)-induced intestinal inflammatory response and gut barrier dysfunction in the mice. Methods: Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact-acceleration head injury. We measured nuclear factor kappa B (NF-kappa B) by electrophoretic mobility shift assay (EMSA); tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA); intercellular adhesion molecule-1 (ICAM-1) by immunohistochernistry; intestinal permeability by lactulose/mannitol (L/M) test; plasma endotoxin by chromogenic limulus amebocyte lysate test. Results: Intestinal levels of NF-kappa B, pro-inflammatory cytokines and ICAM-1 in Nrf2 (-/-)-deficient mice were significantly higher compared with Nrf2 (+/+) mice at 24 h after TBI. Furthermore, higher intestinal permeability and plasma level of endotoxin were observed in the Nrf2 (-/-) mice compared with Nrf2 (+/+) mice. Conclusion: Nrf2 plays an important protective role in limiting intestinal inflammatory response and gut barrier dysfunction after TBI. (C) 2008 Elsevier Ltd. All rights reserved.