Erythropoietin pretreatment ameliorates renal ischaemia-reperfusion injury by activating PI3K/Akt signalling

AimRenal ischaemia-reperfusion (I/R) injury, a primary cause of acute renal failure, can induce high morbidity and mortality. This study aimed to explore the effect of erythropoietin on renal I/R injury and its underlying mechanism. MethodsFifty male Sprague-Dawley rats were randomly allocated to three groups (n=10): the sham group, the renal ischaemia-reperfusion-saline (IRI) group, and the IRI+-Erythropoietin (EPO) group. Erythropoietin (250, 500, 1000U/kg) was intraperitoneally injected 30min before inducing I/R. Renal I/R injury were induced by clamping the left renal artery for 30min followed by reperfusion, along with a contralateral nephrectomy. Renal function and histological damage were determined after 24h reperfusion. The expression of pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 (IL-1), and tumour necrosis factor- (TNF-) in the serum and renal tissue were evaluated by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Further, the effects of erythropoietin on PI3K/Akt signalling, erythropoietin receptor (EPOR) and nuclear factor (NF)-B activation were measured by Western blotting. ResultsErythropoietin pretreatment can significantly decrease the level of renal dysfunction in a dose-dependent manner, attenuated the renal histological changes, the expression of TNF-, IL-1, and IL-6, the levels of reactive oxygen species (ROS) production and NF-B p65 phosphorylation in renal tissue upon IRI. Moreover, erythropoietin pretreatment could further activate the PI3K/Akt signalling and induced EPOR activity. ConclusionsErythropoietin pretreatment could attenuate renal I/R injury by suppressing inflammation, which was associated with activating PI3K/Akt signalling though EPOR activation. Our findings suggest that erythropoietin may be a novel practical strategy to prevent renal I/R injury. Summary at a Glance In this study the authors showed that erythropoietin pretreatment attenuated renal ishcaemia/re-perfusion injury by suppressing inflammation, mainly be activating PI3K/Akt signalling though EPOR activation.