Effects of sildenafil on inflammatory injury of the lung in sodium taurocholate-induced severe acute pancreatitis rats

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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High-Fat Diet Aggravates the Intestinal Barrier Injury via TLR4-RIP3 Pathway in a Rat Model of Severe Acute Pancreatitis

Mediators of Inflammation ◽

10.1155/2019/2512687 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Ying-ru Su ◽

Yu-pu Hong ◽

Fang-chao Mei ◽

Chen-yang Wang ◽

Man Li ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Pancreatitis ◽

Inflammatory Response ◽

Severe Acute Pancreatitis ◽

High Fat Diet ◽

Sodium Taurocholate ◽

Intestinal Barrier ◽

High Body Mass Index ◽

High Fat ◽

Junction Protein

Objective. For patients with severe acute pancreatitis (SAP), a high body mass index (BMI) increases the possibility of infection derived from the intestine. In this study, we evaluate whether TAK242 can alleviate severe acute pancreatitis-associated injury of intestinal barrier in high-fat diet-fed rats. Methods. A SAP model was established by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. Thirty Sprague-Dawley (SD) adult rats were randomly divided into five groups: standard rat chow (SRC) normal (SN), SRC SAP (SAP), high-fat diet normal (HN), HFD SAP (HSAP), and TLR4 inhibitor pretreatment HFD SAP (HAPT) groups. Intraperitoneal injection of 3 mg/kg TAK242 was administered 30 minutes before SAP model establishment in the HAPT group. Rats were sacrificed 12 hours after SAP modeling, followed by blood and pancreatic and distal ileum tissue collection for further analyses. Changes in the pathology responses of the rats in each group were assessed. Result. Analyses of serum amylase, lipase, cholesterol, triglyceride, IL-1β, IL-6, DAO, and serum endotoxin as well as tight junction protein expression including zonula occluden-1 and occludin indicated that high-fat diet aggravated SAP-induced intestinal barrier injury via increasing inflammatory response. In addition, the level of necroptosis was significantly higher in the SAP group compared with the SN group while the HSAP group exhibited more necroptosis compared with the SAP group, indicating the important role of necroptosis in pancreatitis-associated gut injury and illustrating that high-fat diet aggravated necroptosis of the ileum. Pretreatment with TLR4 inhibitor significantly alleviated inflammatory response and reduced necroptosis and level of oxidative stress while improving intestinal barrier function. Conclusion. High-fat diet aggravated SAP-induced intestinal barrier injury via inflammatory reactions, necroptosis, and oxidative stress. Inhibition of TLR4 by TAK242 reduced inflammation, alleviated necroptosis, and lowered the level of oxidative stress and then protected the intestinal barrier dysfunction from SAP in high-fat diet-fed rats.

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Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/129103 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Xian-lin Wu ◽

Jie-xing Li ◽

Zhen-dong Li ◽

Da-sheng Liu ◽

Su-hong Lu ◽

...

Keyword(s):

Acute Pancreatitis ◽

Free Radical ◽

Bile Duct ◽

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Protective Effect ◽

Severe Acute Pancreatitis ◽

Sodium Taurocholate ◽

Multiple Organ ◽

Multiple Organ Dysfunction

Tet is a type of alkaloid extracted fromStephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

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Pioglitazone: A Promising Therapeutic Tool in Sodium Taurocholate-Induced Severe Acute Pancreatitis

Digestive Diseases and Sciences ◽

10.1007/s10620-010-1393-0 ◽

2010 ◽

Vol 56 (4) ◽

pp. 1082-1089 ◽

Cited By ~ 10

Author(s):

Ping Xu ◽

Kai Xu ◽

Jing Wang ◽

Jin-Ping Jiang ◽

Ling-Quan Chen

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Sodium Taurocholate ◽

Therapeutic Tool

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Long noncoding RNA H19 regulates the therapeutic efficacy of mesenchymal stem cells in rats with severe acute pancreatitis by sponging miR-138-5p and miR-141-3p

10.21203/rs.3.rs-34046/v1 ◽

2020 ◽

Author(s):

Guodong Song ◽

Jia Zhou ◽

Ruimei Song ◽

Dalu Liu ◽

Weidi Yu ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Acute Pancreatitis ◽

Mesenchymal Stem Cells ◽

Severe Acute Pancreatitis ◽

Long Noncoding Rna ◽

Therapeutic Efficacy ◽

Noncoding Rna ◽

Sodium Taurocholate ◽

High Morbidity

Abstract Background: Patients with severe acute pancreatitis (SAP), which is characterized by high morbidity and mortality, account for an increasing medical burden worldwide. We previously found that mesenchymal stem cells (MSCs) could attenuate SAP and that expression of long noncoding RNA H19 (LncRNA H19) was upregulated in rats receiving MSCs. In the present study, we investigated the mechanisms of LncRNA H19 regulating the therapeutic efficacy of MSCs in the alleviation of SAP.Methods: MSCs transfected with LncRNA H19 overexpression and knock down plasmids were intravenously injected into rats 12 h after sodium taurocholate (NaT) administration to induce SAP.Results: Overexpressing LncRNA H19 in MSCs significantly enhanced the anti-inflammatory capacity of the MSCs, inhibited autophagy via promotion of focal adhesion kinase (FAK)-associated pathways, and facilitated cell proliferation by increasing the level of β-catenin in rats with SAP. LncRNA H19 functioned as a competing endogenous RNA by sponging miR-138-5p and miR-141-3p. Knocking down miR-138-5p in MSCs increased the expression of protein tyrosine kinase 2 (PTK2, encoding FAK) to suppress autophagy, while downregulating miR-141-3p enhanced the level of β-catenin to promote cell proliferation.Conclusions: In conclusion, LncRNA H19 effectively increased the therapeutic efficacy of MSCs in rats with SAP via the miR-138-5p/PTK2/FAK and miR-141-3p/β-catenin pathways.

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