A possible mechanism for prevention of intestinal programmed cell death after ischemia-reperfusion injury by hepatocyte growth factor pretreatment.
OBJECTIVE
Intestinal ischemia-reperfusion (IR) injury produces necrosis and apoptosis resulting in tissue loss. The authors have observed previously that pretreatment with hepatocyte growth factor (HGF) attenuates enterocyte apoptosis after IR. This study investigated the effects of HGF on tissue levels of caspase-8, an apoptosis initiator, and caspase-3, an apoptosis effector, in intestinal mucosa after IR.


METHODS
Thirty rats underwent placement of jugular venous catheters connected to osmotic pumps; 15 rats received vehicle, and 15 rats received HGF (150 microg/kg/d). After a 48-hour infusion, 5 rats from each group underwent either 35 minutes of superior mesenteric artery occlusion alone, or ischemia followed by 2 or 6 hours of reperfusion. Mucosal protein was analyzed for caspase-8 and caspase-3 activity. DNA fragmentation was used to measure the presence of apoptosis. Statistical significance was determined using analysis of variance.


RESULTS
After 6 hours of reperfusion, caspase-3 activity was increased significantly in control animals (P <.05). In HGF-pretreated animals, caspase-8 and caspase-3 activities were significantly reduced at 6 hours compared with control animals (P <.05).


CONCLUSIONS
By preventing the activation of enterocyte caspase enzymes, and, thus, reducing apoptosis, HGF may enhance preservation of the intestine after IR injury.
Kuenzler
Keith A
KA
Department of Surgery, A.I. duPont Hospital for Children, Wilmington, DE 19803, USA.
Arthur
L Grier
LG
Schwartz
Marshall Z
MZ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004247:DNA / Q000032:analysis; D020895:Enterocytes / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D007422:Intestines / Q000098:blood supply*; D007583:Jejunum / Q000737:chemistry; D008297:Male; D011292:Premedication / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology
D017228:Hepatocyte Growth Factor; D004247:DNA; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases