Chen Guobing, Li Xiang, Huang Mengbing, Li Mei, Zhou Xiaoshuang, Li Ye, Bai Jie
*Faculty of Environmental Science and Engineering†Medical Faculty, Kunming University of Science and Technology‡The Emergency Intensive Care Unit, The First People's Hospital of Yunnan Province, Kunming, China.
Shock. 2016 Jul;46(1):67-74. doi: 10.1097/SHK.0000000000000570.
Sepsis is the main cause of death in critically ill patients, pathogenesis of which is still unclear. The nuclear factor κB (NF-κB) inflammatory signal pathway mediated by endoplasmic reticulum stress is involved in sepsis. Thioredoxin-1 (Trx-1) is an important protein of regulating oxidative stress. It plays a crucial role in the anti-oxidation, anti-apoptosis, and anti-inflammation. However, the role and the mechanism of Trx-1 in sepsis have not been extensively studied. In the present study, we showed that the survival was longer in sepsis induced by cecal ligation and puncture in Trx-1 overexpression transgenic (Tg) mice compared with wild-type mice. Wet/dry lung weight ratio was decreased in Trx-1 Tg mice. The levels of TNF-α and IL-1β in plasma and lung tissue were inhibited in Tg mice. The expressions of glucose-regulated protein 78, inositol-requiring enzyme 1α (IRE1α), tumor necrosis factor receptor-associated factor 2, C/EBP homologous protein, NF-κB, and inhibitors of NF-κBα were increased in lung tissue. More importantly, the overexpression of Trx-1 in transgenic mice suppressed NF-κB inflammatory signal pathway by inhibiting the activation of molecules involved in ER stress. Our results suggest that Trx-1 may play protective role in extending survival in sepsis by regulating inflammatory response through suppressing ER stress.
脓毒症是危重症患者死亡的主要原因，其发病机制尚不清楚。内质网应激介导的核因子κB（NF-κB）炎症信号通路参与脓毒症。硫氧还蛋白-1（Trx-1）是调节氧化应激的重要蛋白。它在抗氧化、抗凋亡和抗炎中起关键作用。然而，Trx-1在脓毒症中的作用及机制尚未得到广泛研究。在本研究中，我们发现与野生型小鼠相比，Trx-1过表达转基因（Tg）小鼠经盲肠结扎穿刺诱导的脓毒症生存期更长。Trx-1 Tg小鼠的肺湿/干重比降低。Tg小鼠血浆和肺组织中TNF-α和IL-1β水平受到抑制。肺组织中葡萄糖调节蛋白78、肌醇需求酶1α（IRE1α）、肿瘤坏死因子受体相关因子2、C/EBP同源蛋白、NF-κB及NF-κBα抑制剂的表达增加。更重要的是，转基因小鼠中Trx-1的过表达通过抑制内质网应激相关分子的激活来抑制NF-κB炎症信号通路。我们的结果表明，Trx-1可能通过抑制内质网应激调节炎症反应，从而在脓毒症中延长生存期发挥保护作用。
