Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China.
J Zhejiang Univ Sci B. 2014 Mar;15(3):281-8. doi: 10.1631/jzus.B1300147.
The signaling pathway for tumor necrosis factor-α (TNF-α) and its receptors is up-regulated during extracorporeal circulation (ECC), and recruits blood neutrophil into the lung tissue, which results in acute lung injury (ALI). In this study, we evaluated the role of tumor necrosis factor receptor 1 (TNFR1) in ECC-induced ALI by blocking TNF-α binding to TNFR1 with CAY10500. Anesthetized Sprague-Dawley (SD) rats were pretreated intravenously with phosphate buffered saline (PBS) or vehicle (0.3 ml ethanol IV) or CAY10500, and then underwent ECC for 2 h. The oxygenation index (OI) and pulmonary inflammation were assessed after ECC. OI was significantly decreased, while TNF-α and neutrophil in bronchoalveolar lavage fluid (BALF) and plasma TNF-α increased after ECC. Pretreatment of CAY10500 decreased plasma TNF-α level, but did not decrease TNF-α levels and neutrophil counts in BALF or improve OI. Lung histopathology showed significant alveolar congestion, infiltration of the leukocytes in the airspace, and increased thickness of the alveolar wall in all ECC-treated groups. CAY10500 pretreatment slightly reduced leukocyte infiltration in lungs, but did not change the wet/dry ratio in the lung tissue. Blocking TNF-α binding to TNFR1 by CAY10500 intravenously slightly mitigates pulmonary inflammation, but cannot improve the pulmonary function, indicating the limited role of TNFR1 pathway in circulating inflammatory cell in ECC-induced ALI.
肿瘤坏死因子-α（TNF-α）及其受体的信号通路在外周循环（ECC）期间上调，并招募血液中性粒细胞进入肺组织，导致急性肺损伤（ALI）。在这项研究中，我们通过用 CAY10500 阻断 TNF-α与 TNFR1 的结合来评估 TNFR1 在 ECC 诱导的 ALI 中的作用。麻醉的 Sprague-Dawley（SD）大鼠静脉预先用磷酸盐缓冲盐水（PBS）或载体（0.3ml 乙醇 IV）或 CAY10500 预处理，然后进行 2 小时的 ECC。ECC 后评估氧合指数（OI）和肺炎症。ECC 后，OI 明显下降，而支气管肺泡灌洗液（BALF）和血浆 TNF-α中的 TNF-α和中性粒细胞增加。CAY10500 的预处理降低了血浆 TNF-α水平，但没有降低 BALF 中的 TNF-α水平和中性粒细胞计数，也没有改善 OI。肺组织病理学显示所有 ECC 治疗组均出现明显的肺泡充血、气腔白细胞浸润和肺泡壁增厚。CAY10500 预处理轻度减少肺内白细胞浸润，但不改变肺组织的湿/干比。静脉内用 CAY10500 阻断 TNF-α与 TNFR1 的结合可轻微减轻肺炎症，但不能改善肺功能，表明 TNFR1 通路在外周循环炎症细胞中在 ECC 诱导的 ALI 中作用有限。
