Department of Anesthesiology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
Department of Anesthesiology, Clinical Medical School of Yangzhou University, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, P.R. China.
Mol Med Rep. 2020 Feb;21(2):607-614. doi: 10.3892/mmr.2019.10851. Epub 2019 Nov 26.
Ventilator‑induced lung injury (VILI) is a life‑threatening condition caused by the inappropriate use of mechanical ventilation (MV). However, the precise molecular mechanism inducing the development of VILI remains to be elucidated. In the present study, it was revealed that the calcineurin/NFATc4 signaling pathway mediates the expression of adhesion molecules and proinflammatory cytokines essential for the development of VILI. The present results revealed that a high tidal volume ventilation (HV) caused lung inflammation and edema in the alveolar walls and the infiltration of inflammatory cells. The calcineurin activity and protein expression in the lungs were increased in animals with VILI, and NFATc4 translocated into the nucleus following calcineurin activation. Furthermore, the translocation of NFATc4 and lung injury were prevented by a calcineurin inhibitor (CsA). Thus, the present results highlighted the critical role of the calcineurin/NFATc4 signaling pathway in VILI and suggest that this pathway coincides with the release of ICAM‑1, VCAM‑1, TNF‑α and IL‑1β.
呼吸机相关性肺损伤（VILI）是由机械通气（MV）使用不当引起的危及生命的病症。然而，诱导 VILI 发展的确切分子机制仍有待阐明。在本研究中，发现钙调神经磷酸酶/NFATc4 信号通路介导了粘附分子和促炎细胞因子的表达，这些分子和细胞因子对于 VILI 的发展至关重要。本研究结果显示，大潮气量通气（HV）可引起肺泡壁的炎症和水肿，以及炎症细胞的浸润。在患有 VILI 的动物中，肺中的钙调神经磷酸酶活性和蛋白表达增加，并且 NFATc4 在钙调神经磷酸酶激活后易位到细胞核中。此外，钙调神经磷酸酶抑制剂（CsA）可阻止 NFATc4 的易位和肺损伤。因此，本研究结果强调了钙调神经磷酸酶/NFATc4 信号通路在 VILI 中的关键作用，并表明该通路与 ICAM-1、VCAM-1、TNF-α 和 IL-1β 的释放一致。
