[The effect of hyperbaric oxygen on acute pancreatitis through downregulating hypoxia-inducible factor.].
OBJECTIVE
To observe the therapeutic effect of hyperbaric oxygen (HBO) on acute pancreatitis (AP) by downregulating hypoxia-inducible factor (HIF).


METHODS
Forty Wistar rats were randomly divided into 4 groups (n = 10): sham group, AP group, normo-oxygen group (NP) and HBO group. At 4 hours after taurocholate-induced AP, the rats of NP group and HBO group were respectively treated with oxygen or HBO for 90 min. Several parameters were measured to evaluate oxygen stress after treatment including oxygen saturation (SaO2), partial pressure of oxygen (PO2), pH, and serum LDH. Pancreatic tissues were subjected to histopathological analysis, immunostained, and homogenized for Western blotted analysis of HIF-1alpha and VEGF, and measuring myeloperoxidase activity. The serum TNF-alpha and pancreatic histopathological scores were evaluated the severity of AP.


RESULTS
It was proved by immunohistochemisty that HIF in acinar cell and polymorphonuclear leukocytes (PMNs) was activated and transferred from cytoplasm into nucleus in AP group, NP group, and HBO group, following upregulation of VEGF. HBO therapy elevated blood SaO2 (99.6% +/- 0.7% vs. 87.7% +/- 1.8% or 91.2% +/- 2.5%, P < 0.05) and PaO2 [(369.1 +/- 67.6) mm Hg (1 mm Hg = 0.133 kPa) vs. (86.6 +/- 5.6) mm Hg or (99.9 +/- 4.0) mm Hg, P < 0.05]. HBO therapy attenuated the severity of AP through inhibiting AP-induced upregulation of HIF-1alpha and VEGF, as evidenced by reducing histopathological scores (12.40 +/- 1.21 vs. 16.45 +/- 1.10 or 16.38 +/- 1.10, P < 0.05), dry/wet weight ratio of pancreatic tissues, and myeloperoxidase activity.


CONCLUSIONS
HIF-1alpha plays a key role in the pathogenesis of AP. HBO therapy attenuates the severity of AP through downregulating the expression of HIF-1alpha.
Bai
Xue-Wei
XW
Department of Hepatobiliary and Pancreatic Surgery, the First Associated Hospital of Harbin Medical University, Harbin 150001, China.
Sun
Bei
B
Wang
Feng
F
Pan
Shang-Ha
SH
Xue
Dong-Bo
DB
Zhu
Hong
H
Jiang
Hong-Chi
HC
D000818:Animals; D006931:Hyperbaric Oxygenation; D010100:Oxygen; D010195:Pancreatitis / Q000628:therapy; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D010100:Oxygen