Effect of peritoneal lavage with ulinastatin on the expression of NF-κB and TNF-α in multiple organs of rats with severe acute pancreatitis

To develop a severe acute pancreatitis (SAP) model transited from mild symptoms, we investigated a “two-hit” strategy with L-arginine in mice. The mice were intraperitoneally injected with ice-cold L-arginine (4 g/kg) twice at an interval of 1 h on the first day and subjected to the repeated operation 72 h afterwards. The results showed the “two-hit” strategy resulted in the destructive damage and extensive necrosis of acinar cells in the pancreas compared with the “one-hit” model. Meanwhile, excessive levels of pro-inflammatory mediators, namely IL-6 and TNF-α, were released in the serum. Remarkably, additional deleterious effects on multiple organs were observed, including high intestinal permeability, kidney injury, and severe acute lung injury. Therefore, we confirmed that the SAP animal model triggered by a “two-hit” strategy with L-arginine was successfully established, providing a solid foundation for a deeper understanding of SAP initiation and therapy research to prevent worsening of the disease.

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Protective effects of Panax notoginseng saponins in a rat model of severe acute pancreatitis occur through regulation of inflammatory pathway signaling by upregulation of miR-181b

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738418818630 ◽

2018 ◽

Vol 32 ◽

pp. 205873841881863

Author(s):

Ming-wei Liu ◽

Yun-qiao Huang ◽

Ya-ping Qu ◽

Dong-mei Wang ◽

Deng-yun Tang ◽

...

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Rat Model ◽

Therapeutic Potential ◽

Sodium Taurocholate ◽

Panax Notoginseng ◽

Serum Levels ◽

Panax Notoginseng Saponins ◽

Tnf Α ◽

Anti Inflammatory

Panax notoginseng saponins are extracted from Chinese ginseng— Panax notoginseng Ledeb—and are known to have therapeutic anti-inflammatory effects. However, the precise mechanism behind their anti-inflammatory effects remains relatively unknown. To better understand how Panax notoginseng saponins exert their therapeutic benefit, we tested them in a rat model of severe acute pancreatitis (SAP). Rats received a tail vein injection of Panax notoginseng saponins and were administered 5% sodium taurocholate 2 h later. Pancreatic tissue was then harvested and levels of miR-181b, FSTL1, TREM1, TLR4, TRAF6, IRAK1, p-Akt, p-p38MAPK, NF-κBp65, and p-IκB-α were determined using Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assays were used to determine serum levels of tumor necrosis factor-α (TNF-α), TREM1, interleukin (IL)-6, ACAM-1, IL-8, and IL-12 and DNA-bound levels of NF-KB65 and TLR4 in pancreatic and ileum tissue. Serum levels of lipase and amylase, pancreatic myeloperoxidase (MPO) activity, and pancreatic water content were also measured. Hematoxylin and eosin staining was used for all histological analyses. Results indicated upregulation of miR-181b, but negligible levels of FSTL1, p-p38MAPK, TLR4, TRAF6, p-Akt, IRAK1, TREM1, p-NF-κBp65, and p-IκB-α, as well as negligible DNA-bound levels of NF-KB65 and TLR4. We also observed lower levels of IL-8, IL-6, ACAM-1, TNF-α, MPO, and IL-12 in the Panax notoginseng saponin–treated group when compared with controls. In addition, Panax notoginseng saponin–treated rats had significantly reduced serum levels of lipase and amylase. Histological analyses confirmed that Panax notoginseng saponin treatment significantly reduced taurocholate-induced pancreatic inflammation. Collectively, our results suggest that Panax notoginseng saponin treatment attenuated acute pancreatitis and pancreatic inflammation by increasing miR-181b signaling. These findings suggest that Panax notoginseng saponins have therapeutic potential in the treatment of taurocholate-induced SAP.

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Effect of Laparoscopic Peritoneal Lavage and Drainage and Continuous Venovenous Diahemofiltration on Severe Acute Pancreatitis

Journal of Laparoendoscopic & Advanced Surgical Techniques ◽

10.1089/lap.2016.0637 ◽

2017 ◽

Vol 27 (11) ◽

pp. 1145-1150 ◽

Cited By ~ 4

Author(s):

Guiliang Wang ◽

Hai Liu ◽

Linfang Xu ◽

Ping Wen ◽

Jianbo Wen ◽

...

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Peritoneal Lavage ◽

Laparoscopic Peritoneal Lavage

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Peritoneal Lavage for Severe Acute Pancreatitis: A Systematic Review of Randomised Trials

World Journal of Surgery ◽

10.1007/s00268-010-0665-3 ◽

2010 ◽

Vol 34 (9) ◽

pp. 2103-2108 ◽

Cited By ~ 17

Author(s):

Zhiyong Dong ◽

Maxim S. Petrov ◽

Jing Xu ◽

Satyanarayan Shanbhag ◽

John A. Windsor ◽

...

Keyword(s):

Systematic Review ◽

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Peritoneal Lavage ◽

Randomised Trials

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A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits

Gut ◽

10.1136/gut.43.2.232 ◽

1998 ◽

Vol 43 (2) ◽

pp. 232-239 ◽

Cited By ~ 75

Author(s):

M O Osman ◽

J U Kristensen ◽

N O Jacobsen ◽

S B Lausten ◽

B Deleuran ◽

...

Keyword(s):

Acute Pancreatitis ◽

Acute Lung Injury ◽

Lung Injury ◽

Severe Acute Pancreatitis ◽

Pancreatic Necrosis ◽

Interleukin 8 ◽

Systemic Complications ◽

Duct Ligation ◽

Tnf Α

Background—Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis.Aims—To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis.Methods—Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis.Results—Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor α (TNF-α) from three to six hours after induction of acute pancreatitis (p=0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-α, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose.Conclusion—WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-α, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.

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Effect of intra-abdominal infection on immunological function and HMGB1/TLR4/NF-κB signaling pathway in patients with severe acute pancreatitis

European Journal of Inflammation ◽

10.1177/2058739218820225 ◽

2018 ◽

Vol 16 ◽

pp. 205873921882022

Author(s):

Cuihong Qin ◽

Ya Li ◽

Ruifeng Song ◽

Feng Xu

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Diamine Oxidase ◽

Apache Ii Score ◽

Control Group ◽

Immunological Function ◽

Infection Group ◽

Abdominal Infection ◽

Tnf Α ◽

Intra Abdominal Infection

The aim of this article is to investigate the effects of intra-abdominal infection on immunological function and high-mobility group box 1 protein (HMGB1)/toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in patients with severe acute pancreatitis (SAP). Clinical data of SAP patients were retrospectively analyzed. SAP patients were divided into intra-abdominal infection group (103 SAP patients) and control group (115 SAP patients without intra-abdominal infection). All patients were evaluated with the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Enzyme-linked immunosorbent assay (ELISA) assays were used to detect the levels of serum endotoxin, d-lactate, diamine oxidase, IgG, IgM, IgA, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and HMGB1. Western blotting was performed to detect the levels of TLR4 and NF-κB in peripheral blood lymphocytes. Compared with control group, the APACHE II score (12.60 ± 3.81 vs 9.55 ± 3.02) and serum endotoxin (0.33 ± 0.15 vs 0.19 ± 0.09 EU/mL), d-lactate (4.33 ± 0.16 vs 4.02 ± 0.12 mg/L), and diamine oxidase (3.88 ± 0.16 vs 3.65 ± 0.13 EU/mL) levels in intra-abdominal infection group were increased significantly (all P < 0.001); serum IgG (7.33 ± 0.82 vs 9.05 ± 0.90 g/L), IgM (1.04 ± 0.49 vs 1.18 ± 0.53 g/L), and IgA (1.65 ± 0.79 vs 1.96 ± 0.88 g/L) levels in intra-abdominal infection group were decreased significantly, while serum IL-1β (118.55 ± 17.04 vs 83.61 ± 12.28 ng/L), IL-6 (12.05 ± 7.69 vs 9.89 ± 6.77 ng/L), TNF-α (25.61 ± 8.76 vs 19.20 ± 8.33 ng/L), and HMGB1 (48.91 ± 20.63 vs 32.74 ± 17.05 μg/L) levels were increased significantly (all P < 0.05); TLR4 and NF-κB in intra-abdominal infection group were increased significantly (both P < 0.001). The intra-abdominal infection can lead to intestinal barrier dysfunction, aggravated inflammatory response, and immune dysfunction in SAP patients, which may be related to the activation of HMGB1/TLR4/NF-κB pathway caused by intra-abdominal infection.

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