Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou, China.
Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, China.
Shock. 2023 Sep 1;60(3):400-409. doi: 10.1097/SHK.0000000000002173. Epub 2023 Jul 6.
Nonantibody-mediated transfusion-related acute lung injury (TRALI) may account for up to 25% of TRALI cases. This indicates the need for further research to understand the pathophysiological mechanisms involved beyond antibody mediation fully. During this research, a TRALI rat model was developed using the trauma-blood loss-massive transfusion method. The severity of pulmonary edema was checked via measurement of lung histopathological changes and the amount of Evans blue dye fluid and bronchoalveolar lavage fluid protein leakage. In addition, potential mechanisms of pathophysiological pathways and inflammation cascades were investigated in TRALI rats in vivo . The findings indicated that TRALI increased inflammatory cytokines and triggered elevated levels of high-mobility group box 1 (HMGB1)/receptor-interacting protein kinase 3 (RIP3), apoptosis protein, and mRNAs in the TM (TRALI model) group as opposed to the normal control. Furthermore, TRALI activated the toll-like receptor 4/nuclear factor kappa B and mitogen-activated protein kinase signaling pathways, which partially regulated the inflammatory response in the TRALI rats. A significant increase was observed in the inflammatory mediators HMGB1 and RIP3 during the early stages of TRALI, suggesting that these mediators could be used as diagnostic markers for TRALI. In addition, HMGB1 and RIP3 promoted the inflammatory response by stimulating the toll-like receptor 44/nuclear factor kappa B and mitogen-activated protein kinase signaling pathways in the lung tissue of rats. Identifying efficient agents from inflammatory mediators such as alarmin can be an innovative scheme for diagnosing and preventing TRALI. These findings give HMGB1 and RIP3 a strong theoretical and experimental foundation for clinical use.
非抗体介导的输血相关急性肺损伤（TRALI）可能占 TRALI 病例的 25%。这表明需要进一步研究，以充分了解抗体介导之外的病理生理机制。在这项研究中，使用创伤-失血-大量输血的方法建立了 TRALI 大鼠模型。通过测量肺组织病理学变化、伊文思蓝染料液和支气管肺泡灌洗液蛋白漏出量来检查肺水肿的严重程度。此外，还在体内研究了 TRALI 大鼠的病理生理途径和炎症级联的潜在机制。研究结果表明，TRALI 增加了炎症细胞因子，并引发了 TRALI 模型组中高迁移率族蛋白 B1（HMGB1）/受体相互作用蛋白激酶 3（RIP3）、凋亡蛋白和 TM 中的 mRNAs 水平升高。此外，TRALI 激活了 Toll 样受体 4/核因子 kappa B 和丝裂原活化蛋白激酶信号通路，部分调节了 TRALI 大鼠的炎症反应。TRALI 早期炎症介质 HMGB1 和 RIP3 显著增加，表明这些介质可作为 TRALI 的诊断标志物。此外，HMGB1 和 RIP3 通过刺激大鼠肺组织中的 Toll 样受体 4/核因子 kappa B 和丝裂原活化蛋白激酶信号通路，促进了炎症反应。从警报素等炎症介质中寻找有效的药物可能是诊断和预防 TRALI 的创新方案。这些发现为 HMGB1 和 RIP3 的临床应用提供了强有力的理论和实验基础。
