Down-regulation of hypoxia-inducible factor-1alpha by hyperbaric oxygen attenuates the severity of acute pancreatitis in rats.
OBJECTIVE
This study investigated the role of hypoxia-inducible factor 1alpha (HIF-1alpha) in acute pancreatitis (AP) and whether HIF-1alpha is involved in the therapeutic effects of hyperbaric oxygen (HBO) on AP.


METHODS
Thirty Wistar rats with taurocholate-induced AP were randomly assigned to 3 groups (each group had 10 rats) receiving oxygen, HBO, or no therapeutic treatment 4 hours after induction. Ten healthy sham-operated rats also served as controls. The arterial oxygen saturation, PaO2, pH, lactate dehydrogenase in the arterial sera, and amylase and tumor necrosis factor alpha in the venous sera were measured 6 hours after induction. Pancreatic tissues were subjected to histopathologic analysis, immunohistochemical and Western-blotted analyses of HIF-1alpha and vascular endothelial growth factor, and measuring of myeloperoxidase activity.


RESULTS
The HBO therapy attenuated the severity of acute pancreatitis; reduced histopathologic scores, dry weight-wet weight ratio of pancreatic tissues, and levels of amylase and lactate dehydrogenase; and elevated blood arterial oxygen saturation, PaO2, and pH values. The HBO therapy inhibited AP-induced up-regulation of HIF-1alpha and its downstream effector vascular endothelial growth factor and the production of tumor necrosis factor alpha and myeloperoxidase activity.


CONCLUSIONS
Hypoxia-inducible factor 1alpha plays a key role in the pathogenesis of AP, and the ability to down-regulate the expression of HIF-1alpha may partially explain the therapeutic effect of HBO on AP.
Bai
Xuewei
X
Hepatosplenic Surgery Center, Department of General Surgery, The First Clinical Medical School of Harbin Medical University, Harbin, China.
Sun
Bei
B
Pan
Shangha
S
Jiang
Hongchi
H
Wang
Feng
F
Krissansen
Geoffrey W
GW
Sun
Xueying
X
D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation; D006931:Hyperbaric Oxygenation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D013656:Taurocholic Acid; D009195:Peroxidase