| Objective:This research use renal ischemia-reperfusion injury(IRI)rat model to explore whether erythropoietin attenuates renal IRI in rats and thepossible pretective mechanism.Methods:72 male Wistar rats were randomized tothe following three groups: Sham operation group(group 1,n=24, in this group,24rats were divide into four subgroups according to the time of harvestingsample,each subgroup has 6 rats),Ischemia-reperfusion group (group 2,n=24,in thisgroup,24 rats were divide into four subgroups according to the time ofreperfusion,that is 1h,6h,12h,24h after reperfusion,each subgroup has 6 rats),rHuEPO treatment group(group 3,n=24,24 rats were divide into four subgroups asgroup 2). Rats were anesthesized and undertook lapotomy. Sham operation groupwere treated without occlusion of left renal artery,only right-nephrectomized. Ingroup2 and group 3,right nephrectomy was performed as soon as occlusion of leftrenal artery for 45 minutes and then recanalization. rHuEPO were administeredintravenously at a dose of 3000U/Kg 5 minutes before reperfusion in group 3. Therats in other two groups were IV normal saline equivalently. When the experimentwas finished, left nephrectomy was performed in every group ,at the sametime ,blood samples were obtained for measurement of serum levels of creatine(Cr)and blood urea nitrogen(BUN). On one hand , 0.5g of every left kidney wasobtained for measurement of tissue malondialdehyde(MDA) contents,superoxidedismutase(SOD) activety as well as Myeloperoxidase(MPO) activity.On the otherhand, the other tissue was used for histological examination andmimmuohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1) andP-selectin. Results:(1)Renal function change: Compared with group 1,the serumlevels of BUN in the subgroup of 1h rerperfusion in group 2 is not differentstatistically, and those in other subgroups were higher signifcantly in group 2(P<0.01). The serum levels of Cr in group 2 were significantly higher than thosein group 1 (P<0.01). Compared with group 1, the serum levels of BUN in therHuEPO treatment subgroups of 1h rerperfusion is not different statistically,andthose in other subgroups were higher signifcantly in group 3 (P<0.05,P<0.01).Theserum levels of Cr in the rHuEPO treatment subgroup of 6h rerperfusion was notdifferent statistically from corresponding sham operation subgroup,and the serumlevels of Cr in other subgroups in group 3 were higher signifcantly than those incorresponding sham operation subgroups(P<0.05,P<0.01). Compared withcorresponding subgroups in group 2, the serum levels of BUN and Cr in thesubgroups of 1h reperfusion were not different statistically,and those in othersubgroups were lower signifcantly in group 3(P<0.05,P<0.01). (2)Tissuebiochemical indicator in kidney: The levels of tissue MDA content and tissue MPOactivity in group 2 were significantly higher than those in the correspondingsubgroups of group 1(P<0.05, P<0.01).Compared with group 1,Tissue SODactivity in kidney in the subgroup of 1h rerperfusion didn't decrease significantly,but that in other subgroups increased signifcantly in group 2(P<0.05,P<0.01).Compared with group 1,the level of tissue MDA content in the subgroup of 24hrerperfusion in group 3 was higher signifcantly than that in group 1(P<0.01),.butthose in other subgroups were not different statistically than those in correspondingsham operation subgroups. Compared with corresponding sham operationsubgroups, tissue SOD activity in kidney in the rHuEPO treatment subgroups of 1hrerperfusion didn't decrease significantly, but those in other subgroups decreasedsignifcantly in group 3(P<0.05), tissue MPO activity in kidney in the rHuEPOtreatment subgroups of 1h,12h rerperfusion didn't increase significantly, but thosein other subgroups of group 3 increased signifcantly(P<0.01). At the same time, thelevels of tissue MDA content in the rHuEPO treatment subgroup of 1h reperfusionwas not different statistically from corresponding renal I/R subgroup, and those inthe other subgroups of group 3 were lower signifcantly than corresponding renalI/R subgroups(P<0.05,P<0.01). Tissue MPO activity in every rHuEPO treatmentsubgroup decreased significantly than corresponding renal I/Rsubgroup(P<0.05,P<0.01).Compared with corresponding renal I/R subgroup,tissueSOD activity in the rHuEPO treatment subgroup of 1h reperfusion was notdifferent statistically,but those in other rHuEPO treatment subgroups increasedsignificantly(P<0.05,P<0.01). (2)Renal cellular damages in group 2 showed moresevere than those in group 1.Compared with group 1,expression of P-selectin andICAM-1 in kidney increased significantly in group 2.What's more, comparedwith group 2,renal histologic injury were attenuated significantly by rHuEPO, aswell as expression of renal P-selectin and ICAM-1 was depressed significantly byrHuEPO in group 3. Conclusion: Our results indicate that rHuEPO can attenuaterenal ischemia-reperfusion injury, which may be probably through against oxygenfree radicals damage and inhibition of inflammation mediated by adhesionmolecule.
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