Sander Marcin L, Eulenburg Volker, Maeyashiki Tatsuo, Jang Jae-Hwi, Müller Sarah D, Stehr Sebastian N, Jungraithmayr Wolfgang, Piegeler Tobias
Department of Anesthesiology and Intensive Care, University of Leipzig Medical Center, Leipzig, Germany.
Department of Anesthesiology and Intensive Care, University of Leipzig Medical Center, Leipzig, Germany; Current address: Translational Anesthesiology and Intensive Care, Medical Faculty, University of Augsburg, Augsburg, Germany.
Transplant Proc. 2024 Nov;56(9):2046-2053. doi: 10.1016/j.transproceed.2024.10.020. Epub 2024 Oct 24.
Remote organ dysfunction is common after lung transplantation and might negatively affect the outcome. The local anesthetic ropivacaine was previously demonstrated to attenuate acute rejection after allogeneic lung transplantation in mice. We hypothesized that lung transplantation might result in detectable molecular signs of injury in kidneys and liver and that ropivacaine might attenuate this damage.
Organs from C57BL/6 mice undergoing allogeneic orthotopic single-lung transplantation were procured at postoperative day 5 and analyzed using Western blot and real-time quantitative polymerase chain reaction probing for Src protein tyrosine kinase, STAT3, and bax/bcl-2. During cold ischemia, the allograft had either been flushed with normal saline only or in combination with ropivacaine (1 µM). A nontransplanted group of animals served as the baseline controls.
The allogeneic stimulus induced by transplantation led to an increase in Src-phosphorylation and STAT3-expression in the kidneys and livers of lung-transplanted mice compared to nontransplanted animals. Bax/bcl-2 as a marker of cellular apoptosis was not affected by the transplantation. In contrast to the findings in the transplanted lungs, the addition of ropivacaine did not have an effect on the examined markers of inflammation in the remote organs.
The observed increase in the inflammatory signaling provides first insight into a possible mechanism, by which remote organ dysfunction after lung transplantation might occur.
肺移植后远程器官功能障碍很常见，可能会对预后产生负面影响。先前已证明局部麻醉药罗哌卡因可减轻小鼠同种异体肺移植后的急性排斥反应。我们推测肺移植可能会导致肾脏和肝脏出现可检测到的损伤分子迹象，并且罗哌卡因可能会减轻这种损伤。
在术后第5天获取接受同种异体原位单肺移植的C57BL/6小鼠的器官，并使用蛋白质免疫印迹法和实时定量聚合酶链反应检测Src蛋白酪氨酸激酶、信号转导和转录激活因子3（STAT3）以及bax/bcl-2。在冷缺血期间，同种异体移植物要么仅用生理盐水冲洗，要么与罗哌卡因（1μM）联合冲洗。一组未进行移植的动物作为基线对照。
与未进行移植的动物相比，移植诱导的同种异体刺激导致肺移植小鼠的肾脏和肝脏中Src磷酸化和STAT3表达增加。作为细胞凋亡标志物的Bax/bcl-2不受移植影响。与移植肺中的发现相反，添加罗哌卡因对远程器官中检测的炎症标志物没有影响。
观察到的炎症信号增加首次揭示了肺移植后远程器官功能障碍可能发生的一种潜在机制。
