Intestinal barrier damage, systemic inflammatory response syndrome, and acute lung injury: A troublesome trio for acute pancreatitis

Ge, Peng; Luo, Yalan; Okoye, Chukwuemeka Samuel; Chen, Haiyang; Liu, Jiayue; Zhang, Guixin; Xu, Caiming; Chen, Hailong

doi:10.1016/j.biopha.2020.110770

Cited by 107 publications

(103 citation statements)

References 155 publications

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“…results showed that enteral nutrition including high-lipid signi cantly improved intestinal mucosal barrier and partially lung in ammation (tumor necrosis factor-α and macrophage in ammatory protein-2), but not in oxidation and pathology of the lung in the rats with hemorrhagic shock/resuscitation. The pathological mechanism of lung injury in SAP was multiple and may be involved with pancreatic necrosis, bacteremia, intestinal barrier failure, activation of in ammatory cascades and diffuse alveolar damage [23]. Just as our result, the EEN could improve the intestinal mucosal barrier, but not in lung injury.…”

Section: Discussionsupporting

confidence: 50%

The effect of early enteral nutrition on intestinal mucosal barrier and remote organs in rats with severe acute pancreatitis

Song

Zhan

et al. 2021

Preprint

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Background The mechanism of early enteral nutrition on intestinal mucosal barrier is still not fully understood and the direct evidence to demonstrate the protective effects of early enteral nutrition against remote organs injury induced by severe acute pancreatitis is lacking. Methods Rats were randomly divided into three groups: 1) only flip pancreas and free diet (n = 8); 2) severe acute pancreatitis and total parenteral nutrition (n = 15); 3) severe acute pancreatitis and early enteral nutrition (n = 15). Severe acute pancreatitis was induced by the retrograde injection of pancreaticobiliary duct with sodium taurocholate. Nutritional supplementation was administered starting 12 hours after induction of pancreatitis. The samples were obtained after the treatment of nutrition 72 hours. Results The mortality was not significant difference between the experimental groups. The pathology of ileum and the content of serum diamine oxidase were significantly lower in early enteral nutrition group than total parenteral nutrition group. The expression of tight junction ZO-1, Occludin and Claudin-1 proteins and the intraepithelial CD8+ and TCRγδ+ lymphocytes were significantly higher in early enteral nutrition group than total parenteral nutrition group. The content of the serum amylase and endotoxin were significantly lower in early enteral nutrition group than total parenteral nutrition group. There was a tendency of decreased pancreas and lung pathology scores in early enteral nutrition group, but the difference between total parenteral nutrition and early enteral nutrition groups was not significant. Conclusion The early enteral nutrition could significantly improve the expression of the tight junctions and intraepithelial lymphocytes, accompanied by improved intestinal mucosal barrier and endotoxin, but failed to the pancreas and lung injury compared to total parenteral nutrition in the rat model of severe acute pancreatitis.

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Section: Discussionsupporting

confidence: 50%

The effect of early enteral nutrition on intestinal mucosal barrier and remote organs in rats with severe acute pancreatitis

Song

Zhan

et al. 2021

Preprint

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“…Changes in mucosal permeability may occur because of mucosal damage. Several studies have demonstrated increases in intestinal permeability in patients with SAP and SAP-related infections ( Schietroma et al, 2016 ; Ge et al, 2020 ). The underlying mechanisms include alterations in the expression, localization, and function of tight junction proteins as well as changes in microbiota, active inflammation, and/or proinflammatory cytokines ( Schietroma et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…The injury of the intestinal mucosal barrier during SAP may be related to microcirculation disturbance, excessive release of inflammatory mediators, ischemia–reperfusion injury, and intestinal epithelial cell apoptosis. Therefore, exploring the molecular mechanism of apoptosis, inflammatory response, and oxidative stress in the process of intestinal mucosal barrier injury in SAP may facilitate finding therapeutic drugs ( Ge et al, 2020 ; Li et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis

Wang

Chen

et al. 2022

Front. Pharmacol.

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Background: Endocannabinoid 2-arachidonoylglycerol (2-AG) is an anti-nociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by monoacylglycerol lipase (MAGL). In this study, we investigated the effects of MAGL inhibition on intestinal permeability and explored the possible mechanism.Methods: A rat model of severe acute pancreatitis (SAP) was established. Rats were divided into three groups according to treatment. We analyzed intestinal permeability to fluorescein isothiocyanate-dextran and the levels of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and 2-AG. Hematoxylin and eosin staining was used to assess histological tissue changes. In vivo intestinal permeability was evaluated by transmission electron microscopy. We obtained ileum tissues, extracted total RNA, and applied RNA-sequencing. Sequencing data were analyzed by bioinformatics.Results: Inflammatory factor levels were higher, while 2-AG levels were lower in the SAP group compared with the control group. Administration of JZL184 to rats with SAP increased the levels of 2-AG and lowered the levels of IL-6 and TNF-α. Notably, intestinal permeability was improved by JZL184 as demonstrated by fluorescein isothiocyanate-dextran measurement, hematoxylin and eosin staining, and transmission electron microscopy. RNA-sequencing showed significant transcriptional differences in SAP and JZL184 groups compared with the control group. KEGG analysis showed that the up- or downregulated genes in multiple comparison groups were enriched in two pathways, focal adhesion and PI3K-Akt signaling pathways. Differential alternative splicing (AS) genes, such as Myo9b, Lsp1, and Git2, have major functions in intestinal diseases. A total of 132 RNA-binding proteins (RBPs) were screened by crossing the identified abnormally expressed genes with the reported RBP genes. Among them, HNRNPDL coexpressed the most AS events as the main RBP.Conclusion: MAGL inhibition improved intestinal mucosal barrier injury in SAP rats and induced a large number of differentially expressed genes and alternative splicing events. HNRNPDL might play an important role in improving intestinal mucosal barrier injury by affecting alternative splicing events.

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“…The previous study has confirmed that TNF-α caused severe oxidative stress and activation of caspase pathway, resulting in serious apoptosis and necrosis of the intestinal and cecal cells. In addition, the physical barrier function of the gastrointestinal mucosa can be influenced by great HMGB1 released by necrotic cells [ 64 ]. Follow-up innovational research revealed that cecal resection strikingly promoted TNF-α-induced lethality in mice by halting necroptosis [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Ketamine inhibits TNF-α-induced cecal damage by enhancing RIP1 ubiquitination to attenuate lethal SIRS

Deng

Yang

et al. 2022

Cell Death Discov.

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Systemic inflammatory response syndrome (SIRS) is a sepsis-associated inflammatory state and a self-defense mechanism against specific and nonspecific stimuli. Ketamine influences many key processes that are altered during sepsis. However, the underlying mechanisms remain incompletely understood. In this study, TNF-α-treated mice, as well as HT-29 and L929 cell models, were applied to characterize TNF-α-induced systemic and local cecal tissue inflammatory responses. Behavioral, biochemical, histological, and molecular biological approaches were applied to illustrate the related processes. Mice with TNF-α-induced SIRS showed systemic and local cecal tissue inflammatory responses, as indicated by increased levels of high mobility group box 1 protein (HMGB1), chemokines (C-X-C motif) ligand 10 (CXCL10), interleukin-6 (IL-6), and IL-10, as well as high mortality. Ketamine pretreatment alleviated death rates, symptoms, and the production of inflammatory cytokines induced by TNF-α in mice. Moreover, ketamine also protected the mice from TNF-α-induced cecal damage by suppressing the phosphorylation of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). In addition, our results showed that ketamine efficiently inhibited TNF-α-induced necroptosis in HT-29 and L929 cells. Furthermore, we explored the mechanism using different L929 cell lines. The results displayed that ketamine inhibited TNF-α-induced necroptosis by enhancing RIP1 ubiquitination and reducing the RIP1-RIP3 and RIP3-MLKL interactions, as well as the formation of necrosomes. Thus, our study may provide a new theoretical and experimental basis for treating diseases characterized by SIRS-associated inflammatory factor storms. Moreover, our exploration may provide potential molecular mechanisms and targets for therapeutic intervention and clinical application of ketamine.

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Intestinal barrier damage, systemic inflammatory response syndrome, and acute lung injury: A troublesome trio for acute pancreatitis

Cited by 107 publications

References 155 publications

The effect of early enteral nutrition on intestinal mucosal barrier and remote organs in rats with severe acute pancreatitis

The effect of early enteral nutrition on intestinal mucosal barrier and remote organs in rats with severe acute pancreatitis

Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis

Ketamine inhibits TNF-α-induced cecal damage by enhancing RIP1 ubiquitination to attenuate lethal SIRS

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