Effects of Baicalin and Octreotide on the Serum TNF-α Level and Apoptosis 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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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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Protective Effect of Dachengqi Decoction on Pancreatic Microcirculatory in Severe Acute Pancreatitis via Down-regulating HMGB-TLR-4-IL-23-IL-17A Mediated Neutrophil Activation Though Targeting SIRT1

10.21203/rs.3.rs-711783/v1 ◽

2021 ◽

Author(s):

Jia Wang ◽

Lei Peng ◽

Dan Chang ◽

Da-qing Hong ◽

Jiong Zhang

Keyword(s):

Acute Pancreatitis ◽

Cell Viability ◽

Severe Acute Pancreatitis ◽

Weight Ratio ◽

Related Factors ◽

Serum Lipase ◽

Tnf Α ◽

Wet Weight ◽

Microcirculatory Function

Abstract BackgroundDachengqi decoction (DCQD), one of classic prescription of Chinese herbal medicine has been widely used in clinic to treat severe acute pancreatitis (SAP). The damage of pancreatic microcirculation plays key pathogenesis of SAP. However, little is known about the molecular pharmacological activity of DCQD on pancreatic microcirculation in SAP. Therefore, the purpose of the study attempted to confirm the improvement of DCQD on pancreatic microcirculation is associated with suppressing neutrophil mediated immune-inflammatory response through promoting the inactivation of HMGB1-TLR-4-IL-23-IL-17A axis via targeting the SIRT1 signal pathway in SAP.Material and MethodsSodium taurodeoxycholate and cerulein were used to establish model of SAP in vitro and vivo, respectively. The pancreatic pathological morphology, wet weight ratio, myeloperoxidase (MPO) activity, cell viability and microcirculatory function of the pancreas, as well as serum lipase and amylase expressions were evaluated. The expression levels of SIRT1, acety-HMGB1, TLR-4, HMGB1, IL-23, IL-17A, neutrophil chemokines (KC, LIX, and MIP-2), and inflammation-related factors (IL-6, IL-1β, and TNF-α), the translocation of HMGB1 and the interaction of SIRT-HMGB1 in the pancreas and serum were determined by ELISA real-time PCR, western blotting and immunoprecipitation.ResultsIn-vivo studies showed DCQD or neutralizing antibody (anti-23p19 or anti-IL-17A) could significantly decrease the activity of lipase, amylase, down-regulate the expression of CD68, MPO, wet/weight, IL-1β, IL-6, TNF-α,neutrophil chemokines (KC, LIX, MIP-2 ), alleviate pathological injury, and improve the microcirculatory function of the pancreas in rats with SAP. Moreover, DCQD remarkably augmented SIRT1 expression, promoted SIRT1 and HMGB1 combination, reduced HMGB1 translocation from nuclear to cytoplasm, and alleviated the expression of acetyl-HMGB1, HMGB1, IL-17A, TLR-4 and IL-23 in vitro and vivo with SAP. However, the intervention with EX527 (SIRT1 inhibitor) or r-HMGB1 (recombinant HMGB1) could obliviously reverse the above-mentioned influence of DCQD in SAP. In vitro, we confirmed that DCQD could decrease the acetylation, migration and release of HMGB1, and improve the decline of cell viability, SIRT1, SIRI-HMGB1 combination induced by cerulein with promoting macrophage to release IL-23 through HMGB1/TLR-4. ConclusionDCQD treatment improves SAP-induced pancreatic microcirculatory dysfunction by inhibiting neutrophil-mediated inflammation through the inactivation of HMGB1-TLR-4-IL-23-IL-17A signaling via Targeting SIRT1.Trial registration: No. 365, 2020.

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

10.21203/rs.2.24775/v2 ◽

2020 ◽

Author(s):

Fei-hu Zhang ◽

Hao Hao ◽

Yang Liu ◽

Kai-liang Fan ◽

Wen Dai ◽

...

Keyword(s):

Acute Pancreatitis ◽

Acute Lung Injury ◽

Lung Injury ◽

Severe Acute Pancreatitis ◽

Heme Oxygenase ◽

Heme Oxygenase 1 ◽

Mrna Levels ◽

Tissue Samples ◽

Shenmai Injection ◽

Tnf Α

Abstract Background: To determine the effect of Shenmai injection (SMI) on acute lung injury (ALI) induced by severe acute pancreatitis (SAP) in rats. Methods: Forty male Sprague-Dawley (SD) rats were grouped into 4 categories: SAP group, sham surgery (SS) group, SAP + SMI group, SAP + SMI + Zinc protoporphyrin (ZnPP) group. Rats in the SAP group were intravenously injected with 1.6 ml/kg saline 30 minutes after induction of SAP models. Rats in the SAP + SMI group were intravenously injected with 1.6 ml/kg SMI, while those in the SAP + SMI + ZnPP group rats were intravenously injected with 1.6 ml/kg SMI and 30 mg/kg ZnPP via intraperitoneal injection. Twenty-four hours after SAP induction, the rats were sacrificed. Excised lung tissues were histologically examined, protein concentration in bronchoalvelar lavage fluid (BALF) was measured and lung wet-to-dry (W/D) weight ratio was calculated. The protein and mRNA levels of the tumor necrosis factor (TNF) -α, heme oxygenase (HO) -1 and interleukin (IL) -10 in blood and tissue samples were measured.Results: SMI treatment attenuated SAP-induced ALI as evidenced by lower scores of lung damage compared with untreated SAP group (p＜0.05). SMI also abolished the SAP-induced rise in BALF and W/D ratio protein concentrations (p＜0.05). Moreover, SMI treatment increased HO-1, IL-10 levels but decreased TNF-α level in serum and tissue samples (p＜0.05). However, inhibition of HO-1 expression by ZnPP led to significant inhibition of all the changes.Conclusions: SMI can alleviate SAP-induced ALI through HO-1 upregulation.

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Ulinastatin in combination with glutamine dipeptide reduces serum levels of TNF-α, endotoxin and IL-6 in patients with severe acute pancreatitis

World Chinese Journal of Digestology ◽

10.11569/wcjd.v19.i18.1946 ◽

2011 ◽

Vol 19 (18) ◽

pp. 1946

Author(s):

Dao-Pang Lin ◽

Zhi-Yun Deng ◽

Xiao-Dong He ◽

Quan Cui ◽

Xiao-Lei Zhao ◽

...

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Serum Levels ◽

Tnf Α

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Early versus delayed enteral feeding in acute pancreatitis

International Surgery Journal ◽

10.18203/2349-2902.isj20180808 ◽

2018 ◽

Vol 5 (3) ◽

pp. 942

Author(s):

Manjunath B. D. ◽

Abhishek G.

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Enteral Feeding ◽

Necrotizing Pancreatitis ◽

Length Of Hospital Stay ◽

Feeding Tube ◽

Clinical Findings ◽

Early Enteral Feeding ◽

Multiple Organs ◽

Feeding Group

Background: Early enteral feeding through a nasoenteric feeding tube is often used in patients with acute pancreatitis, as compared to previous notion of pancreatic rest. This study aims to compare various outcomes of early and late enteral feeding in severe acute pancreatitis.Methods: This study was a randomized trial conducted at Victoria hospital, Bengaluru between July 2016 and June 2017. Patients with severe acute pancreatitis were randomized into early enteral feeding and late enteral feeding groups in the ratio of 1:1. Early enteral feeding group were started on oral feeds within 24 hours of admission. Late enteral feeding group were started on oral feeds after 72 hours of admission. Patient demographics, clinical findings, investigations, length of hospital stay, complications were assessed and compared.Results: In 124 out of 132 patients were included who met inclusion criteria. The mean age of patients was 28.6 years. There were 120 males (96.7%) and 4 females (3.2%). There were no significant differences in age, sex ratio and comorbidities between the two groups. Early enteral feeds group showed lesser number of gastrointestinal adverse effects after initiation of enteral feeds, lesser number of days taken to develop full tolerance to enteral feeds, lesser number of days of admission, lesser complications like necrotizing pancreatitis, single or multiple organs failure, lesser number of ICU admissions, requiring mechanical ventilation, including lesser mortality when compared to delayed enteral feeds group.Conclusions: Patients with severe acute pancreatitis can safely be started on early enteral feeds within 24 hours of admission.

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