Hormone Erythropoietin Of Acute Renal Ischemia-reperfusion Injury In The Inflammatory Reaction

Background:Acute kidney injury (AKI) is a common clinical problem, which despite significant advances in critical care medicine and renal replacement therapy is still associated with high morbidity and mortality. The mechanisms underlying AKI are complex. However inflammation plays a major role in the pathophysiology of AKI. The hematopoietic factor erythropoietin (EPO) has recently been recognized to play a extra-hematopoietic role in variety of organs and tissues. The EPO receptor is present in the glomerulus, mesangial and tubular epithelial cells in the kidney. In vitro studies have shown that EPO has direct effects on proliferation and cell death in proximal tubular epithelial cells. In animal experiment EPO attenuates the dysfunction and histological changes associated with ischemia-reperfusion injury. There is increasingly experimental evidence that EPO may be of therapeutic use in AKI. However it is still unclear how EPO affects the inflammatory response in ischemic acute kidney injury.Objectives:To evaluate the therapeutic effect and mechanism of pretreatment with erythropoietin (EPO) on ischemia/reperfusion-induced acute kidney injury with special concern on inflammatory response.Methods:Eighty300-400g male SD rats were randomly assigned into4experimental groups as Sham group (Sham+NS), Sham+EPO group (Sham+EPO) I/R group (IR+NS) and I/R+EPO group (IR+EPO). Before reperf us ion, bilateral kidneys underwent90min ischemia by clamping renal pedicles. A single dose of EPO was injected intraperitoneally5000IU/kg2hrs prior to occlusion. Animals were sacrificed at1,3,6,24and48hrs after reperfusion to obtain kidney and venous blood samples. The serum concentration of Cr and BUN were measured. Inflammatory response was evaluated according to semi-quantitive analysis of tissue TNF-a, IL-6, MCP-1and NF-kB levels by immunohistochemistry method. Results:(1) Following I/R injury SCr and BUN increased significantly (p<0.05).(2) The EPO pretreated animals exhibited improved renal function (p>0.05) compared with I/R group.(3) Immunohistochemistry analysis revealed that ischemia/reperfusion insult markedly increased TNF-a, IL-6, MCP-1and NF-kB levels (p<0.05). All of these indicators exhibited bimodal distribution with first peak at3hrs and second peak at48hrs or later.(4) Inflammatory cytokines, TNF-α, IL-6and MCP-1, were lessened in the IR+EPO group compared with IR+NS group (p>0.05). Similarly NF-kB, a famous inflammatory transcription factor, was diminished in IR+EPO group with statistical significance at3hrs (p<0.05).Conclusion:(1) Ischemia-reperfusion insult caused significant renal injury.(2) EPO appears to attenuate I/R-induced renal dysfunction.(3) EPO probably reduces the renal expression of TNF-a, IL-6and MCP-1, which might be mediated by its NF-kB inhibition.