Jin Wei, Wang Handong, Ji Yan, Hu Qingang, Yan Wei, Chen Gang, Yin Hongxia
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, PR China.
Cytokine. 2008 Oct;44(1):135-40. doi: 10.1016/j.cyto.2008.07.005. Epub 2008 Aug 21.
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.
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-kappaB) by electrophoretic mobility shift assay (EMSA); tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA); intercellular adhesion molecule-1 (ICAM-1) by immunohistochemistry; intestinal permeability by lactulose/mannitol (L/M) test; plasma endotoxin by chromogenic limulus amebocyte lysate test.
Intestinal levels of NF-kappaB, pro-inflammatory cytokines and ICAM-1 in Nrf2 (-/-)-deficient mice were significantly higher compared with Nrf2 (+/+) mice at 24h after TBI. Furthermore, higher intestinal permeability and plasma level of endotoxin were observed in the Nrf2 (-/-) mice compared with Nrf2 (+/+) mice.
Nrf2 plays an important protective role in limiting intestinal inflammatory response and gut barrier dysfunction after TBI.
探讨核因子红细胞2相关因子2（Nrf2）在创伤性脑损伤（TBI）诱导的小鼠肠道炎症反应和肠屏障功能障碍中的作用。
将野生型Nrf2（+/+）和Nrf2（-/-）基因敲除小鼠进行中度严重的重物落体撞击-加速性头部损伤。通过电泳迁移率变动分析（EMSA）检测核因子κB（NF-κB）；通过酶联免疫吸附测定（ELISA）检测肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）；通过免疫组织化学检测细胞间黏附分子-1（ICAM-1）；通过乳果糖/甘露醇（L/M）试验检测肠道通透性；通过鲎试剂显色法检测血浆内毒素。
与Nrf2（+/+）小鼠相比，TBI后24小时，Nrf2（-/-）基因敲除小鼠肠道中NF-κB、促炎细胞因子和ICAM-1水平显著更高。此外，与Nrf2（+/+）小鼠相比，Nrf2（-/-）小鼠肠道通透性和血浆内毒素水平更高。
Nrf2在限制TBI后肠道炎症反应和肠屏障功能障碍方面发挥重要的保护作用。
