Protective effects of heme oxygenase-1 against severe acute pancreatitis via inhibition of tumor necrosis factor-α and augmentation of interleukin-10

• Main Authors: Fei-hu Zhang, Yu-han Sun, Kai-liang Fan, Xiao-bin Dong, Ning Han, Hao Zhao, Li Kong
• Format: Article
• Language: English
• Published: BMC 2017-08-01
• Series: BMC Gastroenterology
• Subjects: Heme oxygenase-1; Severe acute pancreatitis; Oxidative stress; Tumor necrosis factor-α; Interleukin-10
• Online Access: http://link.springer.com/article/10.1186/s12876-017-0651-4

Abstract Background Heme oxygenase-1 (HO-1) is an inducible defense gene which plays a significant role in inflammation. HO-1 protects cells and tissues through the mechanism of anti-oxidation, maintaining microcirculation and anti-inflammation. The aim of the current study is to investigate the role of HO-1 on systemic inflammatory response in severe acute pancreatitis (SAP). Methods Forty male Sprague-Dawley (SD) rats were randomly assigned into four groups: control group (n = 10); SAP group (n = 10), SAP model was induced by retrograde injection of 3% sodium taurocholate through pancreatic duct; HO-1 stimulation group (n = 10), SD rats were injected 75 μg/kg hemin intraperitoneally 30 min after induction of SAP; HO-1 inhibition group (n = 10), SD rats were injected 20 μg/kg Zinc porphyrin (Zn-PP) intraperitoneally 30 min after induction of SAP. After 24 h of SAP establishment, tissues were collected for HO-1, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) mRNA expression, and blood samples were collected for cytokines and biochemical measurements. Meanwhile, the histopathological changes of pancreas and liver tissues were observed. Results The expression of HO-1 mRNA and protein were significantly induced by SAP in rat pancreas and liver. Hemin treatment significantly decreased oxidative stress and TNF-α in plasma and tissues, while the IL-10 was significantly increased. Pancreas and liver injury induced by SAP was markedly attenuated by Hemin treatment. Moreover, inhibition of HO-1 expression by Zn-PP administration aggravated the injury caused by SAP. Conclusions Induction of HO-1 in early SAP may modulate systemic inflammatory response and prevent pancreas and nearby organs such as liver injury through inhibition of TNF-α and augmentation of IL-10.