Ischemia/reperfusion: a clinically relevant model of intestinal injury yielding systemic inflammation
Ischemia/reperfusion: a clinically relevant model of intestinal injury yielding systemic inflammation
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DOI：
10.1016/j.jpedsurg.2004.11.045
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发表时间：
2005-03-01
影响因子：
2.4
通讯作者：
Levine, AD
中科院分区：
文献类型：
--
作者：
Stallion, A;Kou, TD;Levine, AD
背景/目的：多系统器官衰竭(MSOF)是危重病人发病率和死亡率的主要原因。内毒素诱导的脓毒症的动物模型被用来开发治疗方案，到目前为止，这些方案在临床试验中都失败了。由于MSOF的多种病因影响肠道，作者推测，在脓毒症期间，肠道可能是炎症级联反应的可能触发因素。由于小肠缺血再灌流破坏肠道屏障功能，从而激活全身炎症反应，作者评价了一种小鼠缺血/再灌注模型，以研究局部粘膜和上皮损伤的全身反应。方法：C57BL/10和Balb/c小鼠通过结扎肠系膜上动脉造成不同程度的肠缺血。评估动物的存活率以及大体和显微镜下的肠道损伤。结果：最大的缺血性损伤发生在空肠远端和回肠近端。在C57BL/10小鼠中观察到更严重的上皮损伤和跨壁炎症，这与更高的死亡率相关。结论：该模型模拟了临床上观察到的由进行性缺血性损伤引起的肠道损伤，并最终出现全身症状。这种可复制的全身性炎症模型引起了遗传不同动物的不同反应，其结果可能有助于更好地理解MSOF。(C)2005 Elsevier Inc.保留所有权利。
Background/Purpose: Multisystem organ failure (MSOF) is a major cause of morbidity and mortality in the critically ill patient. Animal models of endotoxin-induced sepsis were used to develop therapeutic regimens, which thus far have failed in clinical trials. Because multiple etiologies of MSOF affect the intestine, the authors hypothesized that during sepsis the gut may act as a possible trigger of the inflammatory cascade. As ischemia and reperfusion of the small intestine disrupts gut barrier function, thereby activating systemic inflammatory responses, the authors evaluated a murine model of ischemia/reperfusion to investigate these systemic responses to local mucosal and epithelial injury.Methods: C57BL/10 and Balb/c mice underwent variable amounts of gut ischemia by superior mesenteric artery occlusion. Animals were evaluated for survival as well as gross and microscopic intestinal damage.Results: Maximal ischemic damage occurred in the distal jejunum and proximal ileum. More severe epithelial damage and transmural inflammation were observed in C57BL/10 mice, which correlated with a higher mortality.Conclusions: This model mimics what is observed clinically with intestinal injury resulting from a progressive ischemic insult with eventual systemic manifestations. This reproducible model of systemic inflammation elicits variable responses from genetically different animals, the results of which may lead to a better understanding of MSOF. (c) 2005 Elsevier Inc. All rights reserved.