Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Am J Physiol Lung Cell Mol Physiol. 2019 Sep 1;317(3):L381-L391. doi: 10.1152/ajplung.00253.2018. Epub 2019 Jun 26.
Ghrelin has proven to be protective against sepsis-induced acute lung injury (ALI) via anti-inflammatory effects. However, its mechanisms remain poorly understood. Alveolar macrophages (AMs) play a key role in mediating inflammatory responses during sepsis-induced ALI by secretion of cytokines and chemokines. This study was undertaken to investigate whether ghrelin suppresses inflammatory effects of AMs and therefore may help to attenuate sepsis-induced ALI. A sepsis model in rats was achieved using cecal ligation and puncture. Ghrelin treatment markedly improved histopathological changes in the lungs and reduced pulmonary inflammation in septic rats. NF-κB translocation and p-Akt and inducible nitric oxide synthase (iNOS) activities in AMs from septic rats were suppressed by ghrelin. In vitro data indicated that ghrelin decreased the levels of LPS-induced IL-1β, TNF-α, and IL-6, NF-κB translocation, and iNOS and Akt activities of AMs. Furthermore, the NF-κB/iNOS pathway or Akt signaling was positively correlated with LPS-induced inflammatory production of AMs in vitro. In conclusion, ghrelin exerts a protective role against sepsis-induced ALI probably by reducing the production of inflammatory cytokines from AMs via inhibition of the NF-κB/iNOS pathway or Akt signaling.
胃饥饿素已被证明通过抗炎作用对脓毒症诱导的急性肺损伤（ALI）具有保护作用。然而，其机制仍知之甚少。肺泡巨噬细胞（AMs）通过分泌细胞因子和趋化因子，在脓毒症诱导的 ALI 中发挥关键作用，介导炎症反应。本研究旨在探讨胃饥饿素是否抑制 AMs 的炎症作用，从而有助于减轻脓毒症诱导的 ALI。通过盲肠结扎和穿刺建立大鼠脓毒症模型。胃饥饿素治疗显著改善了脓毒症大鼠肺部的组织病理学变化，并减轻了肺部炎症。胃饥饿素抑制了脓毒症大鼠 AMs 中的 NF-κB 易位和 p-Akt 和诱导型一氧化氮合酶（iNOS）活性。体外数据表明，胃饥饿素降低了 LPS 诱导的 AMs 中 IL-1β、TNF-α 和 IL-6 的水平、NF-κB 易位以及 iNOS 和 Akt 的活性。此外，NF-κB/iNOS 通路或 Akt 信号与体外 LPS 诱导的 AMs 炎症产物呈正相关。总之，胃饥饿素通过抑制 NF-κB/iNOS 通路或 Akt 信号减轻 AMs 中炎症细胞因子的产生，从而对脓毒症诱导的 ALI 发挥保护作用。
