Transcription Factor Nrf2 Plays a Pivotal Role in Protection Against Traumatic Brain Injury-Induced Acute Intestinal Mucosal Injury in Mice
Transcription Factor Nrf2 Plays a Pivotal Role in Protection Against Traumatic Brain Injury-Induced Acute Intestinal Mucosal Injury in Mice
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DOI：
10.1016/j.jss.2008.08.003
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发表时间：
2009-12-01
影响因子：
2.2
通讯作者：
Yin, Hong-Xia
中科院分区：
文献类型：
--
作者：
Jin, Wei;Wang, Han-Dong;Yin, Hong-Xia
背景创伤性脑损伤（Traumatic brain injury，TBI）可引起急性肠粘膜损伤.核因子红细胞2相关因子2（Nrf 2）在许多生理应激过程中具有独特的作用，但其对TBI后肠粘膜损伤的作用仍有待确定。使野生型Nrf 2（+/+）和Nrf 2（-/-）缺陷型小鼠经受中度严重的重量跌落冲击头部损伤。检测TBI后24 h肠黏膜形态学变化、血浆内毒素、肠通透性、细胞凋亡、炎性细胞因子和抗氧化/解毒酶。Nrf 2基因缺陷小鼠对TBI诱导的急性肠粘膜损伤更敏感，其特征在于TBI后肠结构损伤、血浆内毒素、肠通透性和细胞凋亡的增加更高。在Nrf 2缺陷小鼠中肠粘膜损伤的这种恶化与炎性细胞因子如肿瘤坏死因子-α、白细胞介素-1 β和白细胞介素-6的肠mRNA和蛋白质表达增加以及抗氧化剂和解毒酶（包括NAD（P）H：醌氧化还原酶1（NQO 1）和谷胱甘肽S-转移酶α-1（GST-α 1），与TBI后野生型Nrf 2（+/+）对应物比较。我们第一次表明，缺乏Nrf 2的小鼠更容易受到TBI诱导的急性肠粘膜损伤。我们的数据表明，Nrf 2在TBI诱导的肠粘膜损伤中起着重要的作用，可能通过调节炎症细胞因子和诱导抗氧化和解毒酶。(C)2009 Elsevier Inc. All rights reserved.
Background. Traumatic brain injury (TBI) can induce an acute intestinal mucosal injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) has a unique role in many physiological stress processes, but its contribution to intestinal mucosal injury after TBI remains to be determined.Materials and Methods. Wildtype Nrf2 (+/+) and Nrf2 (-/-) deficient mice were subjected to a moderately severe weight-drop impact head injury. Intestinal mucosal morphological changes, plasma endotoxin, intestinal permeability, apoptosis, inflammatory cytokines, and antioxidant/detoxifying enzymes were measured at 24 hours after TBI.Results. Nrf2 deficient mice were found to be more susceptible to TBI-induced acute intestinal mucosal injury, as characterized by the higher increase in gut structure damage, plasma endotoxin, intestinal permeability, and apoptosis after TBI. This exacerbation of intestinal mucosal injury in Nrf2 deficient mice was associated with increased intestinal mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6, and with decreased intestinal mRNA expression and activity levels of antioxidant and detoxifying enzymes including NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha-1 (GST-alpha 1), compared with their wildtype Nrf2 ( +/+) counterparts after TBI.Conclusions. We show for the first time that mice lacking Nrf2 are more susceptible to TBI-induced acute intestinal mucosal injury. Our data suggests that Nrf2 plays an important role in protecting TBI-induced intestinal mucosal injury, possibly by regulating of inflammatory cytokines and inducing of antioxidant and detoxifying enzymes. (C) 2009 Elsevier Inc. All rights reserved.