From the Department of Cardiothoracic Surgery (Y.-S.S., Y.-F.Y.), the Second Xiangya Hospital of Central South University, Changsha, Hunan; Department of Cardiothoracic Surgery (Y.-S.S., Q.-B.M.), Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu; Department of Surgery (W.T.), Yangzhou East Hospital, Yangzhou, Jiangsu; and Department of Cardiothoracic Surgery (Y.-B.Z.), Hangzhou First People's Hospital, Hangzhou, Zhejiang, China.
J Trauma Acute Care Surg. 2014 Jun;76(6):1417-24. doi: 10.1097/TA.0000000000000229.
Inhibition of nuclear factor κB (NF-κB) activation is a well-know strategy to ameliorate ventilation-induced lung injury (VILI). Inhibitory κB kinase (IKK) plays a key role in the regulation of NF-κB activation. In this study, we determined whether inhibition of IKK by an IKK inhibitor exerts lung protection in a rat model of VILI.
Anesthetized and mechanically ventilated Sprague-Dawley rats were randomly assigned to a standard (tidal volume, 8 mL/kg) or high-tidal volume (tidal volume, 25 mL/kg) ventilation group. An IKK inhibitor (IKK 16) or vehicle was administrated 1 hour before the induction of VILI. All groups were ventilated and observed for 5 hours.
High-pressure ventilation caused activation of NF-κB, increased pulmonary inflammatory mediator levels, lung edema, and impairment of gas exchange. The IKK inhibitor treatment significantly reduced these changes and increased interleukin 10 levels, heme oxygenase 1 activity, protein kinase B (Akt) phosphorylation levels, and nuclear amounts of nuclear factor E2-related factor 2 protein.
IKK may be a therapeutic target for VILI. An IKK inhibitor, IKK 16, can dampen VILI in rats. The beneficial effect of the IKK 16 may be mediated through the inhibition of NF-κB pathway and up-regulation of nuclear factor E2-related factor 2-regulated heme oxygenase 1 through the activation of the phosphatidylinositol 3 kinase/Akt.
抑制核因子 κB（NF-κB）的激活是改善通气诱导的肺损伤（VILI）的一种策略。抑制κB 激酶（IKK）在 NF-κB 激活的调节中起关键作用。在这项研究中，我们确定了 IKK 抑制剂是否通过抑制 IKK 在 VILI 的大鼠模型中发挥肺保护作用。
麻醉并机械通气的 Sprague-Dawley 大鼠被随机分配到标准（潮气量，8mL/kg）或大潮气量（潮气量，25mL/kg）通气组。在 VILI 诱导前 1 小时给予 IKK 抑制剂（IKK 16）或载体。所有组均进行通气并观察 5 小时。
高压通气导致 NF-κB 激活，增加肺炎症介质水平，肺水肿和气体交换受损。IKK 抑制剂治疗显著减轻了这些变化，并增加了白细胞介素 10 水平，血红素加氧酶 1 活性，蛋白激酶 B（Akt）磷酸化水平和核因子 E2 相关因子 2 蛋白的核数量。
IKK 可能是 VILI 的治疗靶点。IKK 抑制剂 IKK 16 可减轻大鼠的 VILI。IKK 16 的有益作用可能是通过抑制 NF-κB 途径和通过激活磷脂酰肌醇 3 激酶/Akt 上调核因子 E2 相关因子 2 调节的血红素加氧酶 1 来介导的。
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