Zhu M, Wang L, Yang J, Xie K, Zhu M, Liu S, Xu C, Wang J, Gu L, Ni Z, Xu G, Che M
Department of Critical Care Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Emergency, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Transplant Proc. 2019 Apr;51(3):972-978. doi: 10.1016/j.transproceed.2019.01.059. Epub 2019 Jan 26.
BACKGROUND/AIMS: Kidney ischemia and reperfusion injury could cause microvascular barrier dysfunction, lung inflammatory cascades activation, and programmed cell death of pulmonary endothelium, leading to acute lung injury. Our study aimed at determining whether erythropoietin (EPO) can ameliorate lung dysfunction following renal ischemia and reperfusion (IR) injury and explored the underlying mechanisms.
In vivo, C57BL/6 mice received EPO (6000 U/kg) before right renal vascular pedicles clamping for 30 minutes, followed by 24 hours of reperfusion. The lung histopathologic changes and inflammatory cytokines expression were assessed. In vitro, cultured human umbilical vein endothelial cells were treated with EPO, and apoptosis rate, proliferation capacity, and phosphorylation status of the Janus kinase-signal transducer and activator of transcription 3 (Jak-STAT3) pathway were measured respectively in the presence or absence of lipopolysaccharide stimulation.
In vivo, EPO remarkably attenuated pulmonary interstitial and alveolar epithelial edema caused by renal IR injury. In vitro, the proliferation capacity of human umbilical vein endothelial cells was significantly increased under EPO stimulation, which correlated with changes in Jak-STAT3 signaling.
Our data indicated that EPO is able to ameliorate acute lung tissue damage induced by renal IR, and at least in part, via the Jak-STAT3 pathway.
背景/目的：肾脏缺血再灌注损伤可导致微血管屏障功能障碍、肺部炎症级联反应激活以及肺内皮细胞程序性死亡，进而引发急性肺损伤。我们的研究旨在确定促红细胞生成素（EPO）是否能改善肾缺血再灌注（IR）损伤后的肺功能障碍，并探讨其潜在机制。
在体内实验中，C57BL/6小鼠在右侧肾血管蒂夹闭30分钟前接受EPO（6000 U/kg），随后进行24小时再灌注。评估肺组织病理变化和炎症细胞因子表达。在体外实验中，用EPO处理培养的人脐静脉内皮细胞，分别在有或无脂多糖刺激的情况下测量凋亡率、增殖能力以及Janus激酶-信号转导子和转录激活子3（Jak-STAT3）通路的磷酸化状态。
在体内实验中，EPO显著减轻了肾IR损伤引起的肺间质和肺泡上皮水肿。在体外实验中，EPO刺激下人脐静脉内皮细胞的增殖能力显著增加，这与Jak-STAT3信号的变化相关。
我们的数据表明，EPO能够改善肾IR诱导的急性肺组织损伤，且至少部分是通过Jak-STAT3通路实现的。
