INTRODUCTION Trauma patients who develop multi-organ dysfunction have increased systemic levels of chemotactic cytokines. Ischemia-reperfusion (IR) injury to the gut may play a role. The purpose of this study was to examine chemokine production in a mouse model of mesenteric IR injury. Given the pre-eminent role of the neutrophil, there has been much investigation of the CXC chemokines, but very limited research on the CC and XC chemokines. We hypothesized that intestinal IR injury would induce remote organ injury and enhance serum CC and XC chemokine levels. METHODS Fasted female C57BL6 mice were anesthetized prior to laparotomy. In IR animals, the superior mesenteric artery (SMA) was occluded for 30, 45, or 75 min, while controls underwent sham laparotomy, n = 5-7 per group. After the indicated time point, the incision was closed and the mouse was allowed to recover for six hours. Following euthanasia, serum levels of 15 chemokines (10 CC, 4 CXC, and 1 XC) were assessed and histopathologic analyses performed. RESULTS Seventy-five minutes of SMA occlusion was the key time frame for significant serum cytokine level up-regulation, intestinal and remote organ injury, and neutrophil influx into tissues. With 75 min of intestinal ischemia, significantly elevated serum levels, as compared to shams, were noted for seven CC chemokines: MCP-1, MCP-3, MIP-1β, MIP-3β, eotaxin, MDC, and RANTES. Levels of the XC chemokine lymphotactin also increased. Levels of MIP-2, IP-10, and KC/GRO (CXC chemokines) rose significantly. MIP-1α levels were only significantly increased at 45 min IR. We did not find any significant IR injury-induced changes in levels of MCP-5, MIP-1γ, or GCP-2, at any ischemia time frame. Serum levels of IL-6 correspondingly increased significantly with longer ischemia times. CONCLUSIONS The novel finding of this study is the demonstration of significant systemic increases in the CC chemokines eotaxin, MCP-3, MDC, MIP-3β in a time-dependent manner, along with tissue injury. The data suggest a complex response to IR injury whereby chemokines that are active on a variety of leukocytes may play a role in inducing local and remote tissue injury.

中文翻译：

---

肠系膜缺血-再灌注损伤上调某些CC，CXC和XC趋化因子，并以时间依赖性方式导致多器官损伤。

引言发生多器官功能障碍的创伤患者的趋化性细胞因子全身水平升高。肠缺血再灌注（IR）损伤可能起作用。这项研究的目的是检查肠系膜IR损伤的小鼠模型中趋化因子的产生。考虑到嗜中性粒细胞的杰出作用，已经对CXC趋化因子进行了大量研究，但对CC和XC趋化因子的研究非常有限。我们假设肠道IR损伤会导致远端器官损伤并提高血清CC和XC趋化因子水平。方法在开腹手术前将禁食的雌性C57BL6小鼠麻醉。在IR动物中，肠系膜上动脉（SMA）阻塞30、45或75分钟，而对照组进行假剖腹手术，每组n = 5-7。在指示的时间点之后，切开切口，让小鼠恢复六个小时。安乐死后，评估15种趋化因子（10 CC，4 CXC和1 XC）的血清水平，并进行组织病理学分析。结果SMA闭塞75分钟是明显的血清细胞因子水平上调，肠道和远端器官损伤以及中性粒细胞流入组织的关键时间范围。肠道缺血75分钟后，与CC相比，七种CC趋化因子：MCP-1，MCP-3，MIP-1β，MIP-3β，嗜酸性粒细胞趋化因子，MDC和RANTES血清血清水平显着提高。XC趋化因子淋巴肌动蛋白的水平也增加。MIP-2，IP-10和KC / GRO（CXC趋化因子）的水平显着上升。MIP-1α水平仅在IR 45分钟时显着增加。我们没有发现任何明显的IR损伤引起的MCP-5水平变化，在任何缺血时间范围内，MIP-1γ或GCP-2。随着更长的缺血时间，血清IL-6水平相应地显着增加。结论该研究的新发现是证明CC趋化因子嗜酸性粒细胞趋化因子，MCP-3，MDC，MIP-3β的全身性显着增加具有时间依赖性，并伴有组织损伤。数据表明对IR损伤有复杂的反应，因此对多种白细胞有活性的趋化因子可能在诱导局部和远端组织损伤中起作用。