Objective         To determine the effect of recombinant human erythropoietin (rhEPO) injected at the same dose but different time points on toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signal transduction pathway in rats after renal ischemia reperfusion injury.         Methods        Totally 70 male SD rats were randomly divided into 7 groups (n=10)

sham operation group (S group)

ischemia reperfusion group (IR group)

the group receiving rhEPO in 6 h before ischemia (P6 group

2 000 U/kg rhEPO via tail vein)

the group receiving rhEPO in 2 h before ischemia (P2 group)

the group receiving rhEPO in 0 h before ischemia (P0 group)

the group receiving rhEPO in 2 h after ischemia (A2 group)

and the group receiving rhEPO in 6 h after ischemia (A6 group). The IR injured model was established by resecting the right kidney and blocking left renal artery for 45 min. In 24 h after blocking

all animals were killed and their blood samples and left kidneys were collected. The renal pathological changes were observed by HE staining. Serum levels of BUN and Cr were determined. The expression and distribution of TLR4 and NF-κB p50 in renal tissue were determined by immunohistochemistry assay. Reverse transcriptional-polymerase chain reaction (RT-PCR) was performed to detect the mRNA levels of TLR4 and NF-κB.         Results        Serum levels of BUN (40.63±4.45) and Cr (166.25±7.80)

the paller scores of renal tubule pathologic damage (251.83±12.65)

the protein expression of TLR4 and NF-κB p50 (211.758±17.720 and 212.492±17.989)

and mRNA expression of TLR4 and NF-κB (2.191±0.046 and 0.771±0.069) were significantly higher in IR group than S group (P0.01). While

these indexes were obviously lower in the P6

P2

P0

A2 and A6 groups than the IR group (P0.01). Moreover

the changing trend of the 5 test items was accordant in each group. Among the administrated groups by rhEPO

the 5 test items were markedly lower in P6 and P2 groups than in P0

A2 and A6 groups (P0.01)

and

there was no significant difference in the 5 items between P6 and P2 groups

and among P0

A2 and A6 groups (P0.05).         Conclusion        rhEPO alleviates acute kidney injury caused by kidney ischemia-reperfusion injury

which might be through inhibiting TLR4/NF-κB signal transduction pathway. rhEPO exerts more significant protective effect when given before ischemia than after ischemia.