Combined peri-ischemic administration of B beta(15-42) in treating ischemia reperfusion injury of the mouse kidney

摘要

The disruption of endothelial integrity is a crucial step for the development of vascular leakage and consequently ischemia-reperfusion injury (IRI). Regarding the molecular cell-cell interaction, the fibrinopeptide B beta(15-42) prevents vascular leakage by stabilizing the inter-endothelial junctions via association with the vascular endothelial-cadherin. In a previous study we showed that a renoprotective effect in early IRI may be achieved by intravenous administration of B beta(15-42) at the time of reperfusion. We now aimed to investigate whether additional pre-ischemic application of B beta(15-42) could enhance this effect. Therefore C57BL/6 mice were subjected to 0.5 h bilateral renal ischemia followed by reperfusion. The animals were randomized into 6 groups (n = 6): two control groups treated with i.v. administration of NaCl at reperfusion for 0.5 h (NaCl 1 h) and 2.5 h (NaCl 3 h), two groups with B beta(15-42) at reperfusion for 0.5 h (B beta(rep) 1 h) and 2.5 h (B beta(rep) 3 h), and two groups with administration of B beta(15-42) immediately pre-ischemic as well as at reperfusion for 0.5 h (B beta(peri) 1 h) and 2.5 h (B beta(peri) 3 h). We found that both B beta(rep) and B beta(peri) mice displayed reduced early renal damage compared with NaCl treated mice. However, there was no further reduction of the IR damage through added preischemic application of B beta(15-42). Overall, we detected significantly reduced endothelial activation, lower tissue infiltration of neutrophils as well as lower tissue levels of neutrophil gelatinase-associated lipocalin (NGAL) in all mice treated with B beta(15-42) compared to mice treated with NaCl. Our data confirm the renoprotective effect of B beta(15-42) in the early therapeutic treatment of acute kidney injury due to ischemia and reperfusion. However, a combined pre-and post-ischemic administration of B beta(15-42) appears to provide no additional benefit compared with a sole administration at reperfusion. (C) 2015 Elsevier Inc. All rights reserved.