Pathogenesis Of Acute Necrotizing Pancreatitis Research Articles

Involvement of Interleukin-17A in Pancreatic Damage in Rat Experimental Acute Necrotizing Pancreatitis

Interleukin (IL)-17A is a proinflammatory cytokine, which has recently attracted much interest due to its pathogenic role in various inflammatory conditions such as ischemia/reperfusion injury, chronic inflammation, and autoimmune diseases, but the role of IL-17A in acute pancreatitis remains unclear. This study aimed to investigate the role of IL-17A in experimental acute necrotizing pancreatitis (ANP). We analyzed the expression of IL-17A during the pathogenesis of ANP in vivo induced by 3 % sodium taurocholate (NaTc), by microarray test, quantitative real-time PCR, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. The effects of IL-17A on pancreatic acinar cells and pancreatic stellate cells (PSCs) were further investigated in vitro using recombinant rat IL-17A (rIL-17A). Expression of IL-17A was significantly increased following experimental acute pancreatitis. In addition, rIL-17A induced rat pancreatic acinar cell necrosis and promoted expression of several target genes, including IL-6, IL-1β, CXCL1, CXCL2, and CXCL5, in acinar cells and PSCs. These findings suggest that IL-17A may be involved in pancreatic damage by regulating the expression of inflammatory cytokines and chemokines during experimental acute pancreatitis.

Effects of ORP150 on appearance and function of pancreatic beta cells following acute necrotizing pancreatitis

Pancreatic beta cells produce and release insulin, which decreases the blood glucose level. Endoplasmic reticulum stress caused pancreatic beta cell dysfunction and death in acute necrotizing pancreatitis (ANP). The 150 kD oxygen-regulated protein (ORP150) took part in the process of endoplasmic reticulum stress. This study investigated the effect of ORP150 on appearance and function of pancreatic beta cells in ANP. Acute necrotizing pancreatitis relied on retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. The severity of ANP was estimated by serum amylase, secretory phospholipase A 2, and pancreatic histopathology. The changes in appearance and function of pancreatic beta cells were detected by light and electron microscopy and the levels of serum glucose, insulin, and C-peptide. ORP150 expression was studied using western blot and immunohistochemisty assay. The expression of ORP150 mainly appeared on pancreatic beta cells and decreased gradually during the pathogenesis of ANP. The results of light and electron microscopy indicated pancreatic beta cell dysfunction and death, concomitant with elevation of serum glucose, insulin, and C-peptide in ANP. These results imply a probable role of ORP150 in the changes in appearance and function of pancreatic beta cells following acute necrotizing pancreatitis, through the pathway of endoplasmic reticulum stress.

Influence of Nuclear Factor κB Activation on Inflammatory Mediators of Alveolar Macrophages in Rats With Acute Necrotizing Pancreatitis

AimTo investigate the potential influence of nuclear factor κB (NF-κB) activation on the inflammatory mediators secreted by alveolar macrophages (AMs) in rats with acute necrotizing pancreatitis (ANP) and to evaluate...

Effects of N-acetylcysteine on mRNA expression of monocyte chemotactic protein and macrophage inflammatory protein 2 in acute necrotizing pancreatitis: experiment with rats

To explore the potential role of monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 2 (MIP-2) in the pathogenesis of acute necrotizing pancreatitis (ANP), and to study the effect of N-acetylcysteine (NAC) on the mRNA expression of MCP-1 and MIP-2. Thirty-five SD rats were randomly divided into 3 groups: sham-operation (SO) group (n = 5), acute necrotizing pancreatitis (ANP) group (n = 15), and NAC-pretreated group (n = 15), ANP were induced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. The NAC- groups underwent intraperitoneal injection of NAC 500 mg/kg 30 minutes before the induction of sodium taurocholate. The ANP and NAC groups were re-divided into 3 equal subgroups respectively: 3 h, 6 h, and 12 h subgroups. 3, 6, and 12 hours after the establishment of models heart blood samples were collected from 5 rats from each model group to detect the serum amylase. Then the rats were killed by blood letting with their pancreases taken out. HE staining and microscopy were used to observe the pathological changes of the pancreas. The wet/dry ratio of pancreas was determined. Enzyme histochemical method was used to detect the activity of myeloperoxidase (MPO) in the pancreas. RT-PCR was used to examine the mRNA expression of MCP-1 and MIP-2. The levels of serum amylase, wet/dry ratio of pancreas, pancreatic MPO activity, and histological score of pancreas of the ANP group increased time-dependently, all the levels at different time-points were significantly higher than those of the SO group (all P < 0.01). The expression levels of MCP-1 mRNA at the time points 3, 6, and 12 h of the ANP group were 0.3653 +/- 0.0213, 0.5890 +/- 0.0225, and 0.7164 +/- 0.0275 respectively, all significantly higher than that of the SO group (0.1492 +/- 0.0036, all P < 0.01). The expression levels of MIP-2 mRNA at different time points of the ANP group were 0.3871 +/- 0.0286, 0.6040 +/- 0.0448, and 0.7692 +/- 0.0620 respectively, all significantly higher than that of the SO group (0.1593 +/- 0.0117, all P < 0.01). The intrapancreatic MPO levels at the time points 3 h, 6 h, and 12 h of the NAC group were 0.63 +/- 0.03, 0.88 +/- 0.05, and 1.31 +/- 0.09 respectively, all significantly lower than those of the ANP groups (0.89 +/- 0.03, 1.42 +/- 0.14, and 1.94 +/- 0.07, all P < 0.05). The MCP-1 mRNA expression levels at different time points the NAC group were 0.2497 +/- 0.0168, 0.4457 +/- 0.0097, and 0.6306 +/- 0.0423 respectively, and the MIP-2 mRNA expression levels at the time points 3 h, 6 h, and 12 h of the NAC group were 0.2436 +/- 0.0099, 0.4312 +/- 0.0221, and 0.6302 +/- 0.0288 respectively, all significantly lower than those of the ANP group (all P < 0.05). The pancreatic histological scores at different time points of the NAC group were 3.50 +/- 0.61, 5.60 +/- 0.65, and 7.50 +/- 0.79, all significantly lower than those of the ANP group (5.10 +/- 0.42, 7.50 +/- 0.50, and 9.90 +/- 0.96, all P < 0.05). The MCP-1 mRNA expression and MIP-2 mRNA expression were both correlated with the severity of pancreatic injury (r = 0.76 and 0.82, both P < 0.05). The chemokines of MCP-1 and MIP-2 are overexpressed at the early stage of acute pancreatitis. Both of them may play an important role in the pathogenesis of AP. NAC may have beneficial effects on AP through downregulation of the expression of MCP-1 and MIP-2.

Nuclear factor-kappaB activation on the reactive oxygen species in acute necrotizing pancreatitic rats

To investigate the potential role of nuclear factor kappa-B (NF-kappaB) activation on the reactive oxygen species in rat acute necrotizing pancreatitis (ANP) and to assess the effect of pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-kappaB). Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. Rats were randomly assigned to three groups (10 rats each): Control group, ANP group and PDTC group. At the 6th h of the model, the changes of the serum amylase, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and pancreatic morphological damage were observed. The expressions of inducible nitric oxide (iNOS) were observed by SP immunohistochemistry. And the expressions of NF-kappaB p65 subunit mRNA were observed by hybridization in situ. Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administrated group ((7 170.40+/-1 308.63) U/L vs (4 074.10+/-1 719.78) U/L, P<0.05), ((76.95+/-9.04) micromol/L vs (65.18+/-9.02) micromol/L, P<0.05) respectively. MDA in both ANP and PDTC group rose significantly over that in control group ((9.88+/-1.52) nmol/L, (8.60+/-1.41) nmol/L, vs (6.04+/-1.78) nmol/L, P<0.05), while there was no significant difference between them. SOD levels in both ANP and PDTC group underwent a significant decrease as compared with that in control ((3 214.59+/-297.74) NU/mL, (3 260.62+/-229.44) NU/mL, vs (3 977.80+/-309.09) NU/mL, P<0.05), but there was no significant difference between them. Though they were still higher than those in Control group, pancreas destruction was slighter in PDTC group, iNOS expression and NF-kappaB p65 subunit mRNA expression were lower in PDTC group as compared with ANP group. We conclude that correlation among NF-kappaB activation, serum amylase, reactive oxygen species level and tissue damage suggests a key role of NF-kappaB in the pathogenesis of ANP. Inhibition of NF-kappaB activation may reverse the pancreatic damage of rat ANP and the production of reactive oxygen species.