Miner T J, Tavaf-Motamen H, Stojadinovic A, Shea-Donohue T
Department of Surgery, Walter Reed Army Medical Center, Washington, D.C., USA.
J Surg Res. 1999 Mar;82(1):1-10. doi: 10.1006/jsre.1998.5510.
It has been suggested that multiple sublethal insults are commonly associated with the development of multiple organ failure (MOF). The gut is considered to be pivotal in the pathogenesis of MOF. This study investigated the effects of repeated ischemia-reperfusion of the rat small intestine.
Groups of rats underwent 30 min of superior mesenteric artery occlusion or sham operation followed by 24 h of reperfusion. They then received an additional 30 min of superior mesenteric artery occlusion and 2 h of reperfusion or sham operation. Small intestine was examined for mucosal injury, neutrophil infiltration, goblet cell number, and generation of the eicosanoids, prostaglandin E2, and leukotriene B4. Activation of neutrophils was assessed in systemic venous blood.
Animals subjected to two insults of ischemia-reperfusion demonstrated significantly less mucosal injury than animals undergoing one episode of ischemia and 2 h of reperfusion, despite increased neutrophil infiltration, leukotriene B4, and activated systemic neutrophils. Goblet cell number was elevated in animals 24 h after the first ischemia-reperfusion insult and remained enhanced after the second episode of ischemia-reperfusion.
The initial episode of ischemia-reperfusion caused an adaptive response associated with cytoarchitectural preservation following the subsequent insult. Increased mucus production was associated with mucosal protection. Nevertheless, repeated ischemia-reperfusion potentiated the local inflammatory response and the systemic activation of neutrophils.
有人提出,多种亚致死性损伤通常与多器官功能衰竭(MOF)的发生有关。肠道被认为在MOF的发病机制中起关键作用。本研究调查了大鼠小肠反复缺血再灌注的影响。
将大鼠分组,进行30分钟的肠系膜上动脉闭塞或假手术,随后再灌注24小时。然后,它们接受额外的30分钟肠系膜上动脉闭塞和2小时再灌注或假手术。检查小肠的黏膜损伤、中性粒细胞浸润、杯状细胞数量以及类花生酸、前列腺素E2和白三烯B4的生成。在体循环静脉血中评估中性粒细胞的活化情况。
经历两次缺血再灌注损伤的动物,其黏膜损伤明显少于经历一次缺血和2小时再灌注的动物,尽管中性粒细胞浸润、白三烯B4增加,且体循环中的中性粒细胞被激活。在第一次缺血再灌注损伤后24小时,动物的杯状细胞数量增加,在第二次缺血再灌注后仍保持增加。
首次缺血再灌注发作引发了一种适应性反应,与随后损伤后的细胞结构保存有关。黏液分泌增加与黏膜保护有关。然而,反复缺血再灌注会增强局部炎症反应和中性粒细胞的全身激活。