Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Department of Medicine, and Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Surg Infect (Larchmt). 2020 Nov;21(9):799-806. doi: 10.1089/sur.2019.193. Epub 2020 May 5.
Acute intestinal ischemia-reperfusion injury (AIIRI) is a devastating clinical condition relevant to multiple diseases processes, including sepsis, trauma, transplantation, and burns. An AIIRI is a contributor to the development of multiple organ dysfunction syndrome (MODS). Oncostatin M (OSM)/oncostatin M receptor (OSMR) signaling is an unrecognized and novel candidate pathway for the mediation of MODS. In this study, we hypothesized that OSM mediates the injury mechanism of AIIRI leading to MODS. Wild-type (WT) and OSMR-knockout (OSMR) C57BL/6 mice underwent AIIRI using a well-established model of selective occlusion of the superior mesenteric artery (SMA). Serum cytokine concentrations were measured using a multiplex detection system. Further tissue analysis was conducted with polymerase chain reaction, enzyme-linked immunosorbent assay, Western blots, and histologic review. Survival was significantly higher in WT than in OSMR groups at 30 minutes of ischemia with 2 hours of reperfusion (100% versus 42.9%; P = 0.015). No significant differences in the degree of local intestinal injury was seen in the two groups. In contrast, the degree of lung injury, as evidenced by myeloperixodase activity, was lower in OSMR animals in the early AIIRI groups. There was a greater degree of renal dysfunction in OSMR mice. Oncostatin M mediated interleukin (IL)-10 upregulation, with WT animals having significantly lower IL-10 concentrations (52.04 ± 23.06 pg/mL versus 324.37 ± 140.35 pg/mL; P = 0.046). Oncostatin M signalling is essential during acute intestinal ischemia-reperfusion injury. An OSMR deficiency results in decreased early lung injury but increased renal dysfunction. There was a significantly increased mortality rate after AIIRI in mice with OSMR deficiency. Augmentation of OSM may be a novel immunomodulatory strategy for AIIRI.
急性肠道缺血再灌注损伤（AIIRI）是一种与多种疾病过程相关的破坏性临床情况，包括脓毒症、创伤、移植和烧伤。AIIRI 是多器官功能障碍综合征（MODS）发展的一个促成因素。肿瘤坏死因子样细胞因子 11（OSM）/肿瘤坏死因子样细胞因子 11 受体（OSMR）信号是介导 MODS 的一个未被认识的新候选途径。在这项研究中，我们假设 OSM 介导 AIIRI 的损伤机制，导致 MODS。野生型（WT）和 OSMR 敲除（OSMR）C57BL/6 小鼠通过选择性肠系膜上动脉（SMA）闭塞的成熟模型发生 AIIRI。使用多重检测系统测量血清细胞因子浓度。进一步的组织分析采用聚合酶链反应、酶联免疫吸附试验、Western blot 和组织学检查进行。在缺血 30 分钟和再灌注 2 小时时，WT 组的存活率明显高于 OSMR 组（100%比 42.9%；P=0.015）。两组间局部肠道损伤程度无显著差异。相比之下，在早期 AIIRI 组中，OSMR 动物的肺损伤程度（以髓过氧化物酶活性为指标）较低。OSMR 小鼠的肾功能障碍程度更高。肿瘤坏死因子样细胞因子 11 介导白细胞介素（IL）-10 的上调，WT 动物的 IL-10 浓度显著降低（52.04±23.06pg/mL比 324.37±140.35pg/mL；P=0.046）。肿瘤坏死因子样细胞因子 11 信号在急性肠道缺血再灌注损伤中是必需的。OSMR 缺乏导致早期肺损伤减少，但肾功能障碍增加。在 OSMR 缺乏的小鼠中，AIIRI 后死亡率显著增加。增强 OSM 可能是一种治疗 AIIRI 的新型免疫调节策略。
