Hepatocyte growth factor pretreatment reduces apoptosis and mucosal damage after intestinal ischemia-reperfusion.
OBJECTIVE
Ischemia-reperfusion (IR) injury to the intestine can result in mucosal damage and cellular death. This study was designed to evaluate the protective effects of pretreatment with hepatocyte growth factor (HGF) on intestine after moderate IR injury.


METHODS
Control animals (n = 7) received 48 hours of intravenous saline, and treatment animals (n = 7) received HGF (150 microg/kg/d). After 35 minutes of mesenteric artery occlusion and 120 minutes of reperfusion, serum and jejunal mucosa samples were obtained. Fluorometric assays were performed for hexosaminidase A (HEX A) and beta-glucuronidase (GLUC), enzyme markers of enterocyte necrosis. Apoptosis was quantified by the TUNEL method. Transcription of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was assessed by multiplex reverse transcription polymerase chain reaction (RT-PCR) Statistical analysis was performed using the Student's t test.


RESULTS
After HGF pretreatment, HEX A and GLUC activities were reduced from 543 +/- 28 to 343 +/- 35 nmole/h/mL (P <.01) and 183 +/- 29 to 119 +/- 22 nmole/h/mL (P <.01), respectively. Pretreated animals had a reduced number of apoptotic cells per 10 crypts (33 +/- 11) compared with untreated rats (225 +/- 24) after IR injury (P <.01). Mean IFN-gamma band intensity was lower in HGF-pretreated animals (0.05 +/- 0.02) compared with controls (0.31 +/- 0.09; P <.05).


CONCLUSIONS
Pretreatment with HGF reduces the severe crypt apoptosis and cellular necrosis after IR injury to the intestine. These data suggest that HGF may be beneficial in attenuating IR damage and thus may have significant clinical application.
Kuenzler
Keith A
KA
Department of Surgery, A.I. duPont Hospital for Children, Wilmington, DE 19803, USA.
Pearson
Philip Y
PY
Schwartz
Marshall Z
MZ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005966:Glucuronidase / Q000097:blood; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D054818:Hexosaminidase A; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D001619:beta-N-Acetylhexosaminidases / Q000097:blood
D017228:Hepatocyte Growth Factor; D005966:Glucuronidase; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases