Attenuation of Renal Ischemia and Reperfusion Injury by Human Adrenomedullin and its Binding Protein

被引:35
|
作者
Shah, Kavin G. [1 ,2 ]
Rajan, Derry [1 ,2 ]
Jacob, Asha [1 ,2 ,3 ]
Wu, Rongqian [1 ,2 ,3 ]
Krishnasastry, Kambhampaty [1 ,2 ]
Nicastro, Jeffrey [1 ,2 ]
Molmenti, Ernesto P. [1 ,2 ]
Coppa, Gene F. [1 ,2 ]
Wang, Ping [1 ,2 ,3 ]
机构
[1] N Shore Univ Hosp, Dept Surg, Manhasset, NY 11030 USA
[2] Long Isl Jewish Med Ctr, Manhasset, NY 11030 USA
[3] Feinstein Inst Med Res, Manhasset, NY USA
关键词
renal ischemia and reperfusion injury; adrenomedullin; adrenomedullin binding protein; inflammation; VASOACTIVE HORMONE ADRENOMEDULLIN; MACROPHAGE CELL-LINE; INTENSIVE-CARE-UNIT; ACUTE KIDNEY INJURY; HYPOTENSIVE PEPTIDE; RIFLE CRITERIA; PLASMA-LEVELS; GUT ISCHEMIA; FAILURE; EXPRESSION;
D O I
10.1016/j.jss.2010.03.064
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Acute renal failure secondary to ischemia and reperfusion (I/R) injury poses a significant burden on both surgeons and patients. It carries a high morbidity and mortality rate and no specific treatment currently exists. Major causes of renal I/R injury include trauma, sepsis, hypoperfusion, and various surgical procedures. We have demonstrated that adrenomedullin (AM), a novel vasoactive peptide, combined with AM binding protein-1 (AMBP-1), which augments the activity of AM, is beneficial in various disease conditions. However, it remains unknown whether human AM/AMBP-1 provides any beneficial effects in renal I/R injury. The objective of our study therefore was to determine whether administration of human AM/AMBP-1 can prevent and/or minimize damage in a rat model of renal I/R injury. Methods. Male adult rats were subjected to renal I/R injury by bilateral renal pedicle clamping with microvascular clips for 60 min followed by reperfusion. Human AM (12 mu g/kg BW) and human AMBP-1 (40 mu g/kg BW) or vehicle (52 mu g/kg BW human albumin) were given intravenously over 30 min immediately following the clip removal (i.e., reperfusion). Rats were allowed to recover for 24 h post-treatment, and blood and renal tissue samples were collected. Plasma levels of AM were measured using a radioimmunoassay specific for rat AM. Plasma AMBP-1 was measured by Western analysis. Renal water content and serum levels of systemic markers of tissue injury were measured. Serum and renal TNF-alpha levels were also assessed. Results. At 24 h after renal I/R injury, plasma levels of AM were significantly increased while plasma AMBP-1 was markedly decreased. Renal water content and systemic markers of tissue injury (e.g., creatinine, BUN, AST, and ALT) were significantly increased following renal I/R injury. Serum and renal TNF-alpha levels were also increased post injury. Administration of human AM/AMBP-1 decreased renal water content, and plasma levels of creatinine, BUN, AST, and ALT. Serum and renal TNF-alpha levels were also significantly decreased after AM/AMBP-1 treatment. Conclusion. Treatment with human AM/AMBP-1 in renal I/R injury significantly attenuated organ injury and the inflammatory response. Thus, human AM combined with human AMBP-1 may be developed as a novel treatment for patients with acute renal I/R injury. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:110 / 117
页数:8
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