Inhibition of rat gut reperfusion injury with an agent developed for the mouse. Evidence that amplification of injury by innate immunity is conserved between two animal species.
Inhibition of rat gut reperfusion injury with an agent developed for the mouse. Evidence that amplification of injury by innate immunity is conserved between two animal species.
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使用为小鼠开发的药物抑制大鼠肠道再灌注损伤。
DOI：
10.1152/ajpregu.00380.2009
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
MooreJr,FrancisD
中科院分区：
文献类型：
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作者：
Afnan,Jalil;Ahmadi-Yazdi,Cyrus;Sheu,EricG;Oakes,SeanM;MooreJr,FrancisD
小鼠再灌注损伤发生在特异性 IgM 天然抗体与暴露于缺血组织中的新抗原结合之后。在再灌注前静脉内施用时，模拟损伤中抗体结合位点的肽可防止 IgM 结合。为了确定这种致病序列是否仅限于小鼠，我们测试了该肽在不同物种（大鼠）中预防再灌注损伤的能力。 Sprague-Dawley 大鼠经历 40 分钟的肠系膜缺血，然后再灌注 180 分钟。在再灌注前静脉内施用肽模拟物。使用基于苏木精和曙红切片的评分系统对肠道损伤进行量化。125I标记的白蛋白用于评估局部（肠道）和远端（肺）损伤。经肽处理的动物的肠的宏观外观水肿和出血较少。显微镜分析显示，经过肽治疗的动物的损伤评分显着降低。渗透性数据表明，经过肽治疗的动物的局部和远端损伤显着减少。数据表明，由于给予鼠缺血新抗原的静脉内肽模拟物，大鼠肠道微绒毛损伤、肠道水肿和肠系膜缺血再灌注后的远程损伤得到减轻，表明第二种物种使用类似的缺血新抗原和相应的天然抗体特异性来将再灌注损伤放大至坏死点。这种炎症机制可能适用于高等物种。
Murine reperfusion injury follows binding of specific IgM natural antibodies to neo-antigens exposed in ischemic tissue. Peptides that mimic the site of antibody binding in the injury prevent IgM binding when administered intravenously before reperfusion. To determine whether this pathogenic sequence is restricted to mice, we have tested the ability of the peptide to prevent reperfusion injury in a dissimilar species, the rat. Sprague-Dawley rats were subjected to 40 min of mesenteric ischemia followed by 180 min of reperfusion. The peptide mimic was administered intravenously prior to reperfusion. Gut injury was quantified using a scoring system based on the hematoxylin-and-eosin section.125I-labeled albumin was used to assess local (gut) and remote (lung) injury. The macroscopic appearance of bowel from peptide-treated animals was less edematous and hemorrhagic. Microscopic analysis showed a significantly reduced injury score in peptide-treated animals. Permeability data indicated a significant reduction in local and remote injury in peptide-treated animals. The data demonstrate attenuation of rat gut microvillus injury, of gut edema, and of remote injury following mesenteric ischemia-reperfusion due to administration of an intravenous peptide mimic of a murine ischemia neo-antigen, indicating a second species uses a similar ischemia neo-antigen and corresponding natural antibody specificity to amplify reperfusion injury to the point of necrosis. This mechanism of inflammation is potentially applicable to higher species.