MiR155 Disrupts the Intestinal Barrier by Inducing Intestinal Inflammation and Altering the Intestinal Microecology in Severe Acute Pancreatitis

2021 ◽  
Author(s):  
Xiaoyu Yang ◽  
Jianhua Wan ◽  
Nianshuang Li ◽  
Cong He ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Intestinal Inflammation ◽  
Intestinal Barrier

Restoration of intestinal mucosal in Euphorbia kansui-treated severe acute pancreatitis rats is based on HMGB1/MFG-E8 expression

2020 ◽  
Vol 21 ◽  
Author(s):  
Chengjiang Qiu ◽  
Kairui Liu ◽  
Xuguang Li ◽  
Weirun Chen ◽  
Sheng Zhang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Serum Amylase ◽  
Intestinal Barrier ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Factor ◽  
Apoptotic Cells ◽  
Rat Ileum ◽  
Plasma Endotoxin ◽  
Euphorbia Kansui

Background: The pathogenesis of severe acute pancreatitis (SAP) is mediated substantially by dysfunctions in the intestinal barrier. Euphorbia kansui (EK) is a medicinal plant used widely in traditional Chinese medicine to treat inflammation; however, its efficacy and mechanism of action in SAP treatment is not yet well understood. Objective: To investigate the role of EK in intestinal barrier tissue repair and in the pathogenesis and development of SAP. Methods: The rat SAP model was established by a retrograde injection of sodium taurocholate into the pancreatic bile duct. The SAP model group and the SAP + EK treatment groups were divided into 6 subgroups according to timing: 2, 6, 12, 24, 48, or 72 h after inducing SAP. The progression of the SAP rats and of the rats receiving the EK treatment was evaluated using the ascites volume, serum amylase and plasma endotoxin levels, and histological grading of intestinal mucosal damage. In addition, serum inflammatory factor contents were measured using enzyme-linked immunosorbent assay (ELISA) tests and apoptotic cells in damaged ileum tissue were detected using TUNEL staining. Apoptosis markers and other signaling proteins in intestinal mucosal cells were detected by immunohistochemical assays and then validated by combining these data with quantitative polymerase chain reactions and western blotting. Results: Compared with the results of the SAP model rats, the results of the rats that received EK treatment demonstrated that EK could effectively reduce the ascites volume and serum amylase and plasma endotoxin levels. EK treatment also greatly reduced the abnormal intestinal morphological alterations in the rat SAP model and significantly downregulated the serum contents of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. EK treatment inhibited the elevation of capapse-3, inhibited the decrease of the Bcl-2 protein, and decreased the number of apoptotic cells in rat ileum tissue. Finally, EK treatment abrogated the increase of HMGB1 and the suppression of MFG-E8 protein expression in the SAP + EK rat ileum tissue. Conclusion: EK suppresses SAP pathogenesis by restoring intestinal barrier function and modulating the HMGB1/MFG-E8 signaling axis.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
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.

Tu1915 Intestinal Barrier Dysfunction in Ageing Animals With Acute Pancreatitis: Increased Intestinal Inflammation?

2015 ◽  
Vol 148 (4) ◽  
pp. S-1190 ◽  
Author(s):  
Marcel C. Machado ◽  
Fabiano Pinheiro da Silva ◽  
Debora G. Cunha ◽  
Denise F. Barbeiro ◽  
Ana Maria M. Coelho ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction

scholarly journals Effects of Lipid Peroxidation-Mediated Ferroptosis on Severe Acute Pancreatitis-Induced Intestinal Barrier Injury and Bacterial Translocation

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Deliang Ma ◽  
Pengling Jiang ◽  
Yingjian Jiang ◽  
Hongbo Li ◽  
Dianliang Zhang
Keyword(s):  
Lipid Peroxidation ◽  
Acute Pancreatitis ◽  
Cell Death ◽  
Severe Acute Pancreatitis ◽  
Bacterial Translocation ◽  
Intestinal Barrier ◽  
Immunofluorescent Staining ◽  
Sham Operation ◽  
Sequencing Analysis ◽  
Rdna Sequencing

Ferroptosis is a recently recognized type of regulated cell death characterized by iron- and lipid peroxidation-mediated nonapoptotic cell death. However, whether ferroptosis is involved in severe acute pancreatitis- (SAP-) induced intestinal barrier injury is unknown. The aim of this study was to investigate whether ferroptosis is involved in SAP-induced intestinal barrier injury, particularly intestinal epithelial cell (IEC) death, and determine whether the inhibition of ferroptosis would ameliorate intestinal barrier injury and prevent bacterial translocation (BT). Sodium taurocholate (5%) was retrogradely perfused into the biliopancreatic duct to establish a rat model of SAP. The rats were divided into three groups: sham operation (SO), SAP-induced intestinal barrier injury (SAP), and ferroptosis inhibitor liproxstatin-1 ( SAP + Lip ). Serum indexes were measured in the rats. In addition, the biochemical and morphological changes associated with ferroptosis were observed, including iron accumulation in intestinal tissue, lipid peroxidation levels, and mitochondrial shrinkage. Hematoxylin staining and eosin staining were used to assess histological tissue changes. Western blot, RT-PCR, and immunofluorescent staining were performed to analyze the expression of ferroptosis-related proteins and genes as well as tight junction. BT was detected by 16S rDNA sequencing analysis. The results indicated that ferroptosis was significantly induced in the IECs from rats with SAP and ferroptosis was mediated by lipid peroxidation. The specific lipid peroxidation of IECs clearly upregulated ferroptosis and exacerbated intestinal barrier injury. Furthermore, treatment with liproxstatin-1 lowered the levels of serum damage markers, decreased lipid peroxidation, and alleviated intestinal and acute remote organ injury in SAP rats. In addition, inhibition of ferroptosis reduced BT. Our findings are the first to demonstrate that ferroptosis contributes to SAP-induced intestinal barrier injury via lipid peroxidation-mediated IEC death. These results suggest that ferroptosis is a potential therapeutic target for SAP-induced intestinal barrier injury.

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