Erythropoietin and its derivative protect the intestine from severe ischemia/reperfusion injury in the rat.
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-alpha 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-alpha 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-alpha and IL-6 and decreasing apoptosis.
Mori
Shozo
S
Second Department of Surgery, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Sawada
Tokihiko
T
Okada
Toshie
T
Kubota
Keiichi
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001212:Asialoglycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007410:Intestinal Diseases / Q000517:prevention & control*; D007422:Intestines / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D016019:Survival Analysis
D001212:Asialoglycoproteins; D005765:Gastrointestinal Agents; C500605:asialoerythropoietin; D004921:Erythropoietin