scholarly journals Picroside II Improves Severe Acute Pancreatitis-Induced Hepatocellular Injury in Rats by Affecting JAK2/STAT3 Phosphorylation Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xuehua Piao ◽  
Xiaodan Sui ◽  
Baohai Liu ◽  
Tingfang Cui ◽  
Zinan Qi
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Caspase 3 ◽  
Janus Kinase ◽  
Stress Factors ◽  
Hepatocellular Injury ◽  
Picroside Ii ◽  
Injury Model ◽  
Stat3 Phosphorylation ◽  
Tnf Α

Picroside II is an important ingredient agent in Traditional Chinese medicine and hoped to reduce hepatocellular injury caused by severe acute pancreatitis (SAP). An SAP-induced hepatocellular injury model was established in rats by using pentobarbital sodium. 27 rats were divided into 3 groups: the sham group (SG), model group (MG), and Picroside groups (PG). SAP-induced hepatocellular injury was assessed using hematoxylin and eosin staining. We measured hepatocellular enzymes (amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)), oxidative stress factors (superoxidase dismutase (SOD) and malondialdehyde (MDA)), and inflammatory factors (tumor necrosis factor α (TNF-α), interleukin- (IL-) 6, and IL-10), apoptotic factors (BAX and cleaved caspase 3), and inflammatory signaling (Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), p-JAK2, and p-STAT3) in hepatocellular tissues. The SAP-induced hepatocellular injury model was successfully established. Picroside II treatment repaired hepatocellular injury by reducing the activities of AMY, ALT, and AST; reducing the levels of MDA, TNF-α, IL-1, IL-6, p-JAK2, p-STAT3, BAX, and cleaved caspase 3; and increasing the levels of SOD and IL-10. Picroside II exerted protective function for the SAP-induced hepatocellular injury model. Picroside II improved SAP-induced hepatocellular injury and antioxidant and anti-inflammatory properties by affecting JAK2/STAT3 phosphorylation signaling.

scholarly journals 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

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.

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

Gut ◽  
1998 ◽  
Vol 43 (2) ◽  
pp. 232-239 ◽  
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.

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

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.

scholarly journals Da-Cheng-Qi Decoction Alleviates Intestinal Injury in Rats with Severe Acute Pancreatitis by Inhibiting the JAK2-STAT3 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Wenyin Jin ◽  
Yinfeng Shen
Keyword(s):  
Acute Pancreatitis ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Severe Acute Pancreatitis ◽  
Terminal Ileum ◽  
Intestinal Injury ◽  
Janus Kinase ◽  
Jak2 Inhibitor ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Objective. To investigate the effect of Da-Cheng-Qi decoction (DCQD) on treating intestinal injury in rats with severe acute pancreatitis (SAP), based on the Janus kinase 2 (JAK2)/signal transducers and transcription 3 (STAT3) signaling pathway. Methods. Rats were randomly divided into the SAP group, SAP + ruxolitinib (JAK2 inhibitor) group, SAP + Stattic (STAT3 inhibitor) group, SAP + DCQD group, and sham operation group. They were further divided into 3-hour, 6-hour, 12-hour, and 18-hour subgroups. Levels of amylase and the inflammatory cytokines tumor necrosis factor-α, interleukin 6, interleukin 10, and interleukin 4 in plasma were tested. The messenger ribonucleic acid (mRNA) expression of JAK2 and STAT3 and the protein expression of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) in the pancreas and terminal ileum tissues were examined. Results. Rats with SAP had severe changes in plasma levels of amylase and inflammatory cytokines and showed an overexpression of JAK2 mRNA, STAT3 mRNA, p-JAK2 protein, and p-STAT3 protein in the pancreas and terminal ileum. The events could be downregulated by treatment with DCQD, JAK2 inhibitor, and STAT3 inhibitor. Conclusions. In rats with SAP, DCQD ameliorated inflammatory cytokines and intestinal injury, which may be closely associated with the inhibition of the JAK2/STAT3 signaling pathway.

scholarly journals 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

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.

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

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.

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

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

scholarly journals miR-339-3p regulated acute pancreatitis induced by caerulein through targeting TNF receptor-associated factor 3 in AR42J cells

2020 ◽  
Vol 15 (1) ◽  
pp. 912-922
Author(s):  
Qi Wang ◽  
Shaofeng Liu ◽  
Zhen Han
Keyword(s):  
Acute Pancreatitis ◽  
Protein Expression ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Luciferase Reporter ◽  
Regulation Mechanism ◽  
Tnf Receptor ◽  
Associated Factor ◽  
Tnf Α ◽  
P38 Pathway

AbstractAcute pancreatitis (AP) is an inflammatory disease with high morbidity and mortality. The regulation mechanism of miRNA is involved in the production and development of various diseases, but the regulation mechanism of miRNA in AP is still not fully elucidated. The expression of miR-339-3p was detected using quantitative real-time PCR. The levels of TNF-α, IL-1β, and IL-6 were detected using enzyme-linked immunosorbent assay. Cell apoptosis was measured using flow cytometry. The protein expressions of TNF receptor-associated factor 3 (TRAF3), Bcl-2, C-caspase 3, Bax, p-p38, and p38 were measured using western blot. Luciferase reporter assay and RNA immunoprecipitation assay were applied to ensure that miR-399-3p targeted TRAF3. Caerulein promoted the expression of TNF-α, IL-1β, and IL-6, enhanced the expression of C-caspase 3 and Bax while inhibited Bcl-2 protein expression. Meanwhile, caerulein also reduced the expression of miR-339-3p and induced the expression of TRAF3 in rat pancreatic acinar cells. miR-399-3p transfection inhibited the levels of TNF-α, IL-1β, and IL-6 and C-caspase 3 and Bax protein expression as well as suppressed cell apoptosis, while increased Bcl-2 protein expression in caerulein-induced AP. TRAF3 has been verified as a target of miR-339-3p. Interestingly, the reduction of miR-399-3p inhibited the p38 pathway, which was impaired by the upregulation of TRAF3. In addition, the suppression effects of miR-339-3p on cell inflammation and apoptosis in caerulein-induced AP were reversed by enhancing TRAF3 expression. In this study, in vitro model of AP was characterized by strong inflammation and cell apoptosis. We have first demonstrated the regulatory network of miR-339-3p and TRAF3. Overexpression of miR-339-3p inhibited cell inflammation and cell apoptosis in caerulein-induced AP through modulating TRAF3 expression via the p38 pathway, providing a new therapeutic target in the treatment of AP.

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