Down-Regulation of Hypoxia-Inducible Factor-1[alpha] by Hyperbaric Oxygen Attenuates the Severity of Acute Pancreatitis in Rats.
Bai, Xuewei MD *; Sun, Bei MD, PhD *; Pan, Shangha MSci *; Jiang, Hongchi MD, PhD *; Wang, Feng MD +; Krissansen, Geoffrey W. PhD ++; Sun, Xueying MD, PhD *++
38(5):515-522, July 2009.
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Objectives: This study investigated the role of hypoxia-inducible factor 1[alpha] (HIF-1[alpha]) in acute pancreatitis (AP) and whether HIF-1[alpha] 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-1[alpha] 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-1[alpha] and its downstream effector vascular endothelial growth factor and the production of tumor necrosis factor [alpha] and myeloperoxidase activity.
Conclusions: Hypoxia-inducible factor 1[alpha] plays a key role in the pathogenesis of AP, and the ability to down-regulate the expression of HIF-1[alpha] may partially explain the therapeutic effect of HBO on AP.
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