Down-Regulation of Hypoxia-Inducible Factor-1α by Hyperbaric Oxygen Attenuates the Severity of Acute Pancreatitis in Rats

Bai, Xuewei; Sun, Bei; Pan, Shangha; Jiang, Hongchi; Feng, Wei; Krissansen, Geoffrey W.; Sun, Xueying

doi:10.1097/mpa.0b013e31819cac24

Cited by 19 publications

(23 citation statements)

References 42 publications

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“…HIF-1α expression levels are reportedly upregulated during AP (16,17). HIF-1α was almost undetectable in the lung tissues of the rats in the sham surgery group.…”

Section: Resultsmentioning

confidence: 99%

“…HIF-1α, an upstream transcription factor induced by hypoxia, regulates the subsequent expression of numerous types of proteins in response to the various pathophysiological conditions induced by hypoxia (4,15). Although previous studies have shown that the levels of HIF-1α are upregulated in AP (16,17), a study has also reported that HIF-1α is associated with augmented pulmonary vascular barrier disruption (18). However, the potential role of HIF-1α in lung tissue injury or restoration following the development of PALI remains unclear.…”

Section: Introductionmentioning

confidence: 97%

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Effects of hypoxia-inducible factor-1α and matrix metalloproteinase-9 on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis-associated lung injury

Chen

Shang

et al. 2014

Experimental and Therapeutic Medicine

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The aim of this study was to investigate the effects of hypoxia-inducible factor-1α (HIF-1α) and matrix metalloproteinase-9 (MMP-9) on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis-associated lung injury (PALI). A total of 40 male Sprague-Dawley rats were randomly divided into a sham surgery group (n=10) and three PALI groups, in which acute pancreatitis was induced by the retrograde infusion of 5% sodium taurocholate (1 ml/kg). The PALI groups were as follows: i) Untreated PALI group (n=10); ii) 2-methoxyestradiol (2ME2) group (5 mg/kg body mass; n=10); and iii) 2ME2 group (15 mg/kg body mass; n=10). In the two 2ME2 groups, the HIF-1α inhibitor 2ME2 was administered intraperitoneally 1 h after the induction of AP. The severity of the pancreatitis was evaluated by the serum amylase levels and pathology. The severity of the lung injury was evaluated by the wet/dry ratio, blood gas analysis and pathology. The alveolar-capillary barrier disruption was assessed by Evans blue dye extravasation. The protein and mRNA expression levels of HIF-1α and MMP-9 were studied using enzyme-linked immunosorbent assays (ELISAs), western blot analysis and reverse transcription-polymerase chain reaction. The active tumor necrosis factor-α levels were measured using an ELISA. The HIF-1α inhibitor 2ME2 attenuated the severity of the pancreatitis and PALI, while the lung edema and alveolar-capillary barrier disruption were significantly ameliorated compared with those in the untreated PALI group. Administration of the higher dose of 2ME2 significantly suppressed the protein expression of MMP-9 in the lung tissues. The results indicate that HIF-1α has a major function in alveolar-capillary barrier disruption and lung edema in PALI via a molecular pathway cascade involving MMP-9. Inhibition of HIF-1α by 2ME2 attenuates alveolar-capillary barrier disruption and lung edema. Pharmacological blockade of this pathway in patients with PALI may provide a novel therapeutic strategy.

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“…HIF-1α expression levels are reportedly upregulated during AP (16,17). HIF-1α was almost undetectable in the lung tissues of the rats in the sham surgery group.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Effects of hypoxia-inducible factor-1α and matrix metalloproteinase-9 on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis-associated lung injury

Chen

Shang

et al. 2014

Experimental and Therapeutic Medicine

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show abstract

“…[34][35][36] HIF-1α is one of the most important nuclear factors that adjusts the expression of anaerobic glycolysis key enzyme in inflammatory cells. 33 The present study shows that inhibition of HIF-1α activation can reduce anaerobic glycolysis ability in inflammatory cells and ATP content in cells to weaken the adhesion, chemotaxis, and proinflammatory ability of inflammatory cells.…”

Section: Figurementioning

confidence: 98%

“…38 High expression of VEGF within the lung may contribute to the development of pulmonary edema by deteriorating the state of the adherens junction complexes on the endothelium and aggravate microcirculation disturbance and inflammatory response. 33,39 Our study shows that insulin and insulin/ PEG-b-(PELG-g-PLL) pretreatment can reduce the expression of VEGF through downregulating HIF-1α to decrease the inflammatory response of pulmonary tissues.…”

Section: Figurementioning

confidence: 99%

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The effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(L-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor

Tong¹,

Tang²,

Li³

et al. 2016

IJN

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The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly( l -lysine) block copolymer poly(ethylene glycol)- b -(poly(ethylenediamine l -glutamate)- g -poly( l -lysine)) (PEG- b -(PELG- g -PLL) on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor (HIF) as compared to free insulin. Sprague Dawley rats were pretreated with 30 U/kg insulin or insulin/PEG- b -(PELG- g -PLL) complex, and then subjected to 45 minutes of ischemia and 24 hours of reperfusion. The blood and lungs were collected, the level of serum creatinine and blood urea nitrogen were measured, and the dry/wet lung ratios, the activity of superoxide dismutase and myeloperoxidase, the content of methane dicarboxylic aldehyde and tumor necrosis factor-α, and the expression of HIF-1α and vascular endothelial growth factor (VEGF) were measured in pulmonary tissues. Both insulin and insulin/PEG- b -(PELG- g -PLL) preconditioning improved the recovery of renal function, reduced pulmonary oxidative stress injury, restrained inflammatory damage, and downregulated the expression of HIF-1α and VEGF as compared to ischemia/reperfusion group, while insulin/PEG- b -(PELG- g -PLL) significantly improved this effect.

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Hypoxia

Jain¹

2017

Textbook of Hyperbaric Medicine

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Down-Regulation of Hypoxia-Inducible Factor-1α by Hyperbaric Oxygen Attenuates the Severity of Acute Pancreatitis in Rats

Abstract: 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.

Cited by 19 publications

References 42 publications

Effects of hypoxia-inducible factor-1α and matrix metalloproteinase-9 on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis-associated lung injury

Effects of hypoxia-inducible factor-1α and matrix metalloproteinase-9 on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis-associated lung injury

The effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(L-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor

Hypoxia

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