C5a inhibitor protects against ischemia/reperfusion injury in rat small intestine.
C5a inhibitor protects against ischemia/reperfusion injury in rat small intestine.
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DOI：
10.1111/1348-0421.12338
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发表时间：
2016-01
影响因子：
2.6
通讯作者：
Okada H
中科院分区：
文献类型：
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作者：
Tuboly E;Futakuchi M;Varga G;Érces D;Tőkés T;Mészáros A;Kaszaki J;Suzui M;Imai M;Okada A;Okada N;Boros M;Okada H
急性肠系膜缺血（Acute mesenteric ischemia， AMI）是由相当大的肠道损伤引起的，与肠缺血再灌注有关。为了阐明缺血/再灌注损伤的机制，我们在实验性AMI模型中使用C5a抑制肽AcPepA来检测C5a过敏毒素的作用，诱导炎症细胞和肠上皮细胞的增殖。在这个大鼠模型中，肠系膜上动脉被阻塞，随后再灌注（诱导I/R）。其余各组在缺血或再灌注前给予AcPepA治疗。诱导I/R诱导的肠损伤和AcPepA显著降低了严重损伤绒毛的比例。诱导I/R诱导血管中C5a阳性多形核白细胞和损伤部位附近CD204阳性巨噬细胞的次级受体；这与缺氧诱导因子1 α阳性细胞有关。AcPepA对这些炎症细胞的诱导作用减弱。此外，AcPepA增加绒毛上皮细胞的增殖，可能防止进一步的损伤。因此，诱导I/R激活C5a，随后多形核白细胞和产生缺氧诱导因子1 - α的巨噬细胞的积累，导致绒毛损伤。AcPepA是一种C5a抑制肽，可阻断C5a的有害作用，表明其对实验性AMI的炎症后果具有治疗作用。
Acute mesenteric ischemia (AMI) is caused by considerable intestinal injury, which is associated with intestinal ischemia followed by reperfusion. To elucidate the mechanisms of ischemia/reperfusion injuries, a C5a inhibitory peptide termed AcPepA was used to examine the role of C5a anaphylatoxin, induction of inflammatory cells, and cell proliferation of the intestinal epithelial cells in an experimental AMI model. In this rat model, the superior mesenteric artery was occluded and subsequently reperfused (Induce‐I/R). Other groups were treated with AcPepA before ischemia or reperfusion. Induce‐I/R induced injuries in the intestine and AcPepA significantly decreased the proportion of severely injured villi. Induce‐I/R induced secondary receptor for C5a‐positive polymorphonuclear leukocytes in the vessels and CD204‐positive macrophages near the injured site; this was correlated with hypoxia‐induced factor 1‐alpha‐positive cells. Induction of these inflammatory cells was attenuated by AcPepA. In addition, AcPepA increased proliferation of epithelial cells in the villi, possibly preventing further damage. Therefore, Induce‐I/R activates C5a followed by the accumulation of polymorphonuclear leukocyte and hypoxia‐induced factor 1‐alpha‐producing macrophages, leading to villus injury. AcPepA, a C5a inhibitory peptide, blocks the deleterious effects of C5a, indicating it has a therapeutic effect on the inflammatory consequences of experimental AMI.