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

Abstract

BackgroundHeme 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).MethodsForty 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.ResultsThe 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.ConclusionsInduction 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.

Shenmai injection alleviates acute lung injury in a severe acute pancreatitis rat model via heme oxygenase-1 upregulation

“…Previous studies indicated that HO-1, which protects cells and organs against inflammation-induced injury and oxidative stress, plays an essential role in SAP pathogenesis including many other inflammatory disorders associated with the immune system [35][36][37][38][39]. This study revealed that HO-1 induction during the early stages of SAP development modulated systemic inflammatory response through TNF-α suppression and IL-10 augmentation [20].…”

“…The rats were grouped into four categories (n = 10): SAP group, sham surgery (SS) group, SAP + SMI group, SAP + SMI + Zinc protoporphyrin (ZnPP) group, a specific inhibitor of HO-1 [19]. The SAP model was designed by retrogradely injecting the rats with 4% sodium taurocholate (1 ml/kg) via the pancreatic duct following anaesthetization with sodium pentobarbital (40 mg/kg) [20]. The SAP group rats were intravenously injected with 1.6 ml/kg saline 30 minutes after induction of SAP.…”

“…Paraffin-embedded tissues were sectioned into 5 µm thick sections and stained with hematoxylin and eosin. The sections were visualized under a light microscope [20]. Histopathology scores were calculated based on 3 randomly chosen tissues.…”

“…The expression of β-actin was used for data normalization. The PCR reaction conditions used were; 15 seconds of denaturation at 95℃, 20 seconds of annealing at 60℃, and 30 seconds of extension at 72℃[20].…”

Shenmai injection alleviates acute lung injury in a severe acute pancreatitis rat model via heme oxygenase-1 upregulation

“…Shenmai injection (SMI) is a traditional Chinese medicine comprising Ophiopogonjaponicas (lilia-ceae), and Ginseng Rubra (araliaceae) extracts [18] and is widely used to clinically treat heart diseases, sepsis, osteoarthritis and asthma [19][20][21][22]. SMI is generally considered a safe drug [23,24].…”