Abstract
Background/AimsSevere acute pancreatitis (SAP) is associated with intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS), but treatment of these conditions is difficult. We studied a rat model of SAP + IAH to determine the effect of oral administration of Clostridium butyricum and butyrate (its major metabolite) on intestinal barrier functions.MethodsA total of 48 rats were assigned to four groups, with 12 rats per group: Sham, SAP+IAH, SAP+IAH+C. butyricum, and SAP + IAH + butyrate. SAP was induced by sodium taurocholate infusion into the biliopancreatic duct, intra-abdominal pressure (IAP), mortality was measured 24 h later, and then rats were euthanized. The plasma levels of several markers [amylase, diamine oxidase (DAO), fluorescein isothiocyanate (FITC)-dextran, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, IL-12, lipopolysaccharide (LPS)] and fecal butyric acid level were determined. The pancreas and intestine were examined using histology, and RT-PCR and Western blotting of intestinal tissues were used to measure the expression of six markers {tight junction proteins [zonula occludens protein-1 (ZO-1), claudin-1, claudin-2, occluding], matrix metalloproteinase 9 [MMP9], and TNF-α}. The gut flora of the rats was examined by 16S rRNA sequencing.ResultsInduction of SAP + IAH altered several functions of the intestinal barrier, and enhanced intestinal permeability, decreased the levels of ZO-1, claudin-1, occludin, the richness and diversity of the microflora community, the relative abundance (RA) of Firmicutes, and the number of probiotic organisms. However, induction of SAP+IAH increased the expression of claudin-2, MMP9, and TNF-α, and the RA of Proteobacteria and pathogens in the feces. Rats that received oral C. butyricum or butyrate had reduced intestinal injury and plasma levels of DAO, LPS, and inflammatory cytokines.ConclusionThis study of rats with SAP+IAH indicated that oral dosing of C. butyricum or butyrate reduced intestinal injury, possibly by altering the functions of the intestinal mucosal barrier.
Highlights
Severe acute pancreatitis (SAP), which is characterized by necrosis of pancreatic and peri-pancreatic tissues and often accompanied by multiple organ dysfunction syndrome (MODS), has a mortality rate of 10–30% (Thandassery et al, 2015; Agarwal et al, 2016)
At 24 h after surgical induction of SAP, the intraabdominal pressure (IAP) was 0.8– 4.7 mmHg in the sham operated (Sham) Group, 12.8–22.7 mmHg in the SAP + intraabdominal hypertension (IAH) Group, 12.0–16.4 mmHg in the C. butyricum Group, and 13.1–15.9 mmHg in the Butyrate Group. These results confirm the successful establishment of this rat model of SAP with IAH
Pancreatic tissues had no significant changes in the Sham Group, but there were obvious histopathological changes in the other three groups (Figure 2A)
Summary
Severe acute pancreatitis (SAP), which is characterized by necrosis of pancreatic and peri-pancreatic tissues and often accompanied by multiple organ dysfunction syndrome (MODS), has a mortality rate of 10–30% (Thandassery et al, 2015; Agarwal et al, 2016). Damage of the intestinal barrier is characterized by increased mucosal and vascular permeability, and this can cause translocation of pathogens and endotoxins from the intestinal tract to the regional lymph nodes, portal veins, and peripheral blood system, leading to systemic endotoxemia. These pathogens and endotoxins can promote pancreatic necrosis, increase the release of proinflammatory factors, and cause multiple organ failure (MOF)
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