Objective
To investigate the protective effect of erythropoietin (EPO) and its nonhematopoietic
derivative (asialoEPO) against intestinal ischemia/reperfusion (I/R) injury in a rat
model.
Methods
The superior mesenteric artery of Wistar rats was clamped for 60 minutes and then
released. The rats were divided into 4 groups (n = 15 in each group): sham operation
(Sham), vehicle treatment (Vehicle), EPO treatment (EPO), and asialoEPO treatment
(AsialoEPO). EPO and asialoEPO were administered subcutaneously at 1000 units/kg for
10 minutes before clamping, 30 minutes after the start of clamping, and just before
declamping. This treatment was followed by determination of 72-hour survival rates,
serum TNF-α and IL-6 levels, histologic evaluation of the small intestine, quantification
of the number of apoptotic cells, and analysis of the antiapoptotic molecules Bcl-xL
and XIAP by Western blotting.
Results
The survival rates at 72 hours after I/R injury in the Sham, Vehicle, EPO, and AsialoEPO
groups were 100%, 33%, 75%, and 83%, respectively (P < .05). Blood TNF-α and IL-6 were significantly more suppressed in the EPO and AsialoEPO
groups than in the Vehicle group at 6 hours after I/R injury. Histologically, injury
to villi in the EPO and AsialoEPO groups was significantly less than in the Vehicle
group. The number of apoptotic cells in the EPO and AsialoEPO groups was significantly
less than in the Vehicle group. Western blotting revealed that EPO and asialoEPO constitutively
increased the expression of Bcl-xL.
Conclusions
EPO and asialoEPO exert a strong protective effect against intestinal I/R injury,
possibly by inhibiting release of TNF-α and IL-6 and decreasing apoptosis.
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Article info
Publication history
Accepted:
December 20,
2007
Identification
Copyright
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
