The apoptosis of peripheral blood lymphocytes promoted by hyperbaric oxygen treatment contributes to attenuate the severity of early stage acute pancreatitis in rats

Abstract

The aim of this study was to investigate the immunoregulatory effects of hyperbaric oxygen (HBO) via promoting the apoptosis of peripheral blood lymphocytes (PBLs) to attenuate the severity of early stage acute pancreatitis (AP) in rats. Additionally, the persistence of the HBO treatment effects was evaluated. One hundred and twenty male Wistar rats were randomized into four groups: sham, AP, AP + normobaric oxygen (NBO), and AP + HBO. Each group consisted of 30 rats. Four hours after the induction of AP, the 30 rats in the AP + NBO group were given normobaric oxygen treatment with 100 % oxygen at 1 atm for 90 min. The 30 rats in the AP + HBO group received 100 % oxygen at 2.5 atm for 90 min, with a compression/decompression time of 15 min. The 30 rats in the AP group remained untreated. At 6, 12, and 24 h after the induction of AP, surviving rats from each group were sacrificed, and the blood and tissue samples were collected for the following measurements: the partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) of the arterial blood, the levels of serum amylase, lipase, interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-10 (IL-10), hepatocyte growth factor (HGF), and reactive oxygen species (ROS), and the mitochondrial membrane potential (∆Ψm) of the PBLs. The expression levels of procaspase-3, caspase-3, procaspase-9, and caspase-9 were also evaluated in the PBLs. Additionally, the apoptosis of PBLs was assessed, and the pancreatic tissues were subjected to a histopathological analysis by pathological grading and scoring. The histopathology of the lung, liver, kidney, duodenum, and heart was also analyzed at 12 h after the induction of AP. Significant differences were found at 6 and 12 h after AP induction. The HBO treatment significantly elevated the PaO2 and SaO2 levels, and the ROS levels in the PBLs. Additionally, HBO downregulated the levels of amylase and lipase. The HBO treatment also reduced the ∆Ψm levels, upregulated the expression of caspase-3 and caspase-9, and increased the apoptosis rate of the PBLs. Moreover, the HBO treatment decreased the serum concentrations of IL-2, IFN-γ and HGF, and reduced the pathological scores of the pancreatic tissue. The histopathological changes of the lung, liver, kidney, duodenum, and heart were also improved. A significant elevation of IL-10 occurred only at the 12-h time point. However, no obvious differences were found at the 24-h time point. This study demonstrated that the HBO treatment can promote the apoptosis of PBLs via a mitochondrial-dependent pathway and inhibit the inflammatory response. These immunoregulatory effects may play an important therapeutic role in attenuating the severity of early stage AP. The repeated administration of HBO or the use of HBO in combination with other approaches may further improve outcomes.

Hydrogen sulphide exacerbates acute pancreatitis by over‐activating autophagy viaAMPK/mTOR pathway

“…There was a positive correlation between the incubated level of H 2 S and histological score. The level of HMGB1, a well‐known member of damage‐associated molecular patterns released from the nuclei of necrotic cells , was detected by immunoblot (Fig. C).…”

“…A model of AP in rats was established using the method as previously described . Briefly, the rats were anaesthetized by an intra‐peritoneal injection of sodium pentobarbital (40 mg/kg).…”

A New Combination Therapy in Severe Acute Pancreatitis—Hyperbaric Oxygen Plus 3-Aminobenzamide

“…Hyperbaric oxygen (HBO) therapy also has been investigated in previous experimental studies that have significantly improved TOSp 12 and apoptosis in SAP. 13 , 14 Thereafter, more recent studies by HBO in AP indicated that enhanced inflammatory response, 15 cytokines levels, 16 TOSp, and THSc. 17 , 18 …”

Application of hyperbaric oxygen in liver transplantation

“…Their results showed the peak levels of polymorphonuclear leukocyte elastase (PMNE) and thrombomodulin (TM) were diminished and delayed, and the elevated expression of CD18 (a protein related to leukocyte adhesion) was clearly suppressed after HBO exposure. In the rats with acute pancreatitis, Bai et al (2014) found HBO could induce the apoptosis of peripheral blood lymphocytes to attenuate the disease.…”