Department of Neurosurgery, School of Medicine, Southern Medical University (Guangzhou), Jinling Hospital, Nanjing 210002, Jiangsu Province, China.
J Surg Res. 2013 Jan;179(1):e227-34. doi: 10.1016/j.jss.2012.03.030. Epub 2012 Apr 5.
Traumatic brain injury (TBI) can cause gastrointestinal dysfunction and increase intestinal permeability. Nuclear factor kappa B (NF-κB) has been shown to be associated with these intestinal events, but it is not well known how NF-κB is activated in the intestine after TBI. Based on previous studies, we hypothesize that myeloid differentiation primary response protein 88 (Myd88) may have an important role in NF-κB activation in the intestine, which mediates the inflammation and ultimately results in acute intestinal mucosal injury.
We randomly divided adult male C57BL/6 mice into control groups and TBI groups at different time points. We induced a closed head injury model by weight drop (a 333-g metal rod dropping from a 2.5-cm height). We detected Myd88 protein level and NF-κB binding activity in ileum tissue by Western blot and electrophoretic mobility shift assay, respectively. Meanwhile, we detected the mRNA levels of Myd88, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and intercellular adhesion molecule-1 by real-time polymerase chain reaction.
The Myd88 protein and mRNA levels, as well as NF-κB binding activity in the ileum tissue, significantly increased at 6 h after TBI, peaked at 3 d, and remained elevated by 5 d post-injury. The levels of TNF-α, IL-1β, and intercellular adhesion molecule-1 also remarkably increased after TBI. There was a positive relationship between the expression of Myd88 and that of NF-κB, TNF-α, and IL-1β.
Traumatic brain injury induced a rapid and persistent up-regulation of Myd88, NF-κB, and proinflammatory cytokines in the intestine. This up-regulation which might have an important role in the pathogenesis of acute intestinal mucosal injury.
创伤性脑损伤（TBI）可导致胃肠道功能障碍和增加肠道通透性。核因子 kappa B（NF-κB）已被证明与这些肠道事件有关，但 TBI 后 NF-κB 在肠道中如何被激活尚不清楚。基于先前的研究，我们假设髓样分化初级反应蛋白 88（Myd88）在 NF-κB 在肠道中的激活中可能具有重要作用，该作用介导炎症，最终导致急性肠黏膜损伤。
我们将成年雄性 C57BL/6 小鼠随机分为对照组和 TBI 组，在不同时间点进行实验。我们通过落体（333 克金属棒从 2.5 厘米高度落下）诱导闭合性颅脑损伤模型。我们通过 Western blot 和电泳迁移率变动分析分别检测回肠组织中的 Myd88 蛋白水平和 NF-κB 结合活性，同时通过实时聚合酶链反应检测 Myd88、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和细胞间黏附分子-1 的 mRNA 水平。
TBI 后 6 小时，回肠组织中的 Myd88 蛋白和 mRNA 水平以及 NF-κB 结合活性显著增加，在 3 天达到峰值，并在损伤后 5 天仍保持升高。TNF-α、IL-1β 和细胞间黏附分子-1 的水平在 TBI 后也显著增加。Myd88 的表达与 NF-κB、TNF-α 和 IL-1β 的表达呈正相关。
TBI 诱导肠道中 Myd88、NF-κB 和促炎细胞因子的快速和持续上调。这种上调可能在急性肠黏膜损伤的发病机制中起重要作用。
