scholarly journals Effects of Bacterial Translocation and Autophagy on Acute Lung Injury Induced by Severe Acute Pancreatitis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Hanlin Wang ◽  
Chang Li ◽  
Yingjian Jiang ◽  
Hongbo Li ◽  
Dianliang Zhang
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Lung Tissue ◽  
Bacterial Translocation ◽  
Control Group ◽  
Sham Operation ◽  
Rdna Sequencing

Aim. To reveal the role of bacterial translocation (BT) and autophagy in severe acute pancreatitis-induced acute lung injury (SAP-ALI). Methods. Rats were separated into a control (sham-operation) group (n=10) and a SAP group (n=30). Sodium taurocholate (5%) was retrogradely injected into the cholangiopancreatic duct to induce SAP-ALI in rats. Then, 16S rDNA sequencing was used to detect bacterial translocation (BT). Hematoxylin eosin staining (HE) was used to detect morphological changes to the pancreas, intestine, and lung. And lung tissue wet/dry weight ratio (W/D ratio) was used to assess the extent of pulmonary edema. The expressions of LC3II and Beclin1 proteins were analyzed by western blot and immunofluorescence. Glutathione peroxidase (GPx), malondialdehyde (MDA), and superoxide dismutase (SOD) were used to assess oxidative stress in lung tissue. Results. Levels of TNF-α, IL-6, lipase, and amylase in the SAP group were significantly higher than those in the control group (P<0.01). Histopathological score and W/D ratio of the lung in the SAP-BT(+) group were significantly higher than that in the SAP-BT(-) group (P<0.01). LC3II expression was higher in the SAP-BT(-) group than that in the SAP-BT(+) group (P<0.01). The results were consistent with those of LC3II immunofluorescence assay. The expression of Beclin1 was similar to that of LC3II (P<0.01). MDA content in the SAP-BT(+) group was significantly higher than that in the SAP-BT(-) group (P<0.01), whereas SOD and GPX activities were opposite (P<0.01). Conclusions. BT can aggravate SAP-ALI with the increasing oxidative stress level, which may be related to the decrease of autophagy level.

scholarly journals Sitagliptin activates the p62–Keap1–Nrf2 signalling pathway to alleviate oxidative stress and excessive autophagy in severe acute pancreatitis-related acute lung injury

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Lingming Kong ◽  
Jie Deng ◽  
Xiang Zhou ◽  
Binbin Cai ◽  
Baofu Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Nuclear Translocation ◽  
Signalling Pathway ◽  
Ros Production ◽  
Nrf2 Knockout ◽  
Anti Inflammatory

AbstractAcute lung injury (ALI) is a complication of severe acute pancreatitis (SAP). Sitagliptin (SIT) is a DPP4 inhibitor that exerts anti-inflammatory and antioxidant effects; however, its mechanism of action in SAP-ALI remains unclear. In this study, we investigated the effects of SIT on SAP-ALI and the specific pathways involved in SAP-induced lung inflammation, including oxidative stress, autophagy, and p62–Kelch-like ECH-associated protein 1 (Keap1)–NF-E2-related factor 2 (Nrf2) signalling pathways. Nrf2 knockout (Nrf2−/−) and wild-type (WT) mice were pre-treated with SIT (100 mg/kg), followed by caerulein and lipopolysaccharide (LPS) administration to induce pancreatic and lung injury. BEAS-2B cells were transfected with siRNA-Nrf2 and treated with LPS, and the changes in inflammation, reactive oxygen species (ROS) levels, and autophagy were measured. SIT reduced histological damage, oedema, and myeloperoxidase activity in the lung, decreased the expression of pro-inflammatory cytokines, and inhibited excessive autophagy and ROS production via the activation of the p62–Keap1–Nrf2 signalling pathway and promotion of the nuclear translocation of Nrf2. In Nrf2-knockout mice, the anti-inflammatory effect of SIT was reduced, resulting in ROS accumulation and excessive autophagy. In BEAS-2B cells, LPS induced ROS production and activated autophagy, further enhanced by Nrf2 knockdown. This study demonstrates that SIT reduces SAP-ALI-associated oxidative stress and excessive autophagy through the p62–Keap1–Nrf2 signalling pathway and nuclear translocation of Nrf2, suggesting its therapeutic potential in SAP-ALI.

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.

scholarly journals Daphnetin ameliorates acute lung injury in mice with severe acute pancreatitis by inhibiting the JAK2–STAT3 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shujun Yang ◽  
Yaodong Song ◽  
Qiaofang Wang ◽  
Yanna Liu ◽  
Zhongwei Wu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Lung Tissue ◽  
Tissue Damage ◽  
Coumarin Derivative ◽  
Janus Kinase ◽  
Stat3 Signalling ◽  
Lung Tissue Damage

AbstractSevere acute pancreatitis (SAP) is often associated with pulmonary inflammation leading to acute lung injury. Daphnetin, a natural coumarin derivative, has been reported to exert anti-inflammatory effects. Here, we explored the effect and possible mechanism of daphnetin in a mouse model of SAP-associated lung injury induced by an intraperitoneal injection of l-arginine. The severity of pancreatic and lung injury is determined by histology and its score. Immunostaining of inflammatory and apoptotic cells was used to demonstrate lung tissue inflammation and apoptosis; ELISA analysis of serum and tissue cytokine levels; and western blotting and immunohistochemical staining for the activated Janus kinase 2 (JAK2)–signal transducer and activator of transcription protein 3 (STAT3) signalling pathway in lung tissues. Daphnetin pretreatment significantly reduced SAP-induced pancreatic and lung tissue damage, reduced interleukin-6 and tumour necrosis factor-α concentrations in both serum and lung tissues, reduced serum amylase and myeloperoxidase activities, and reduced macrophage (CD11b) and neutrophil (Ly6G) infiltration and cell apoptosis in the lung tissue. Moreover, SAP-induced phosphorylation of JAK2 and STAT3 in the lung tissue was also significantly diminished by the daphnetin pretreatment. These results indicated that daphnetin reduces SAP-associated lung tissue damage, likely by inhibiting the activation of JAK2–STAT3 signalling.

scholarly journals Astragaloside IV Synergizing with Ferulic Acid Ameliorates Pulmonary Fibrosis by TGF-β1/Smad3 Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jiahuan Tong ◽  
Zhisong Wu ◽  
Yuchen Wang ◽  
Qingxun Hao ◽  
Haoge Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Fibrosis ◽  
Ferulic Acid ◽  
Lung Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Sham Operation ◽  
Astragaloside Iv ◽  
Group A ◽  
Tgf Β1

Objective. The study aims to research the interventional effect and mechanism of astragaloside IV (Ast) synergizing with ferulic acid (FA) on idiopathic pulmonary fibrosis (IPF) induced by bleomycin in mice. Methods. The mice were randomly divided into seven groups with 10 mice in each group, namely, a sham operation group, a model group, a miRNA-29b (miR-29) group, a miR-29b negative control group (NC group), a FA group, an Ast group, and a combination group. A mouse model of pulmonary fibrosis was established by intratracheal instillation of bleomycin. Samples were collected after 28 days of continuous administration. Hematoxylin and eosin (HE) and Masson staining were used to observe pathological changes in the lung tissue, and the degree of fibrosis was evaluated using the hydroxyproline content. Changes in transforming growth factor-β1 (TGF-β1) and Smad3 in the lung were observed using immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in the serum. PCR was used to detect the expression of the miR-29b, TGF-β1, Smad3, and nuclear factor E2-related factor 2 (Nrf2) genes. Western blotting was used to detect the content of the TGF-β/Smad3 protein. Results. Ferulic acid combined with astragaloside IV reduced the degree of pulmonary fibrosis and the synthesis of hydroxyproline in lung tissue. The combination of the two also regulated the oxidative stress response ， TGF-β1/Smad3 pathway and miR-29b in lung tissue. Conclusion. Astragaloside IV combined with ferulic acid regulated the oxidative stress of lung tissues and TGF-β1/Smad3 signaling through miR-29b, thereby reducing the degree of pulmonary fibrosis. This provides a reference direction for the clinical treatment of IPF patients.

Effects of penehyclidine hydrochloride on severe acute pancreatitis-associated acute lung injury in rats

2018 ◽  
Vol 97 ◽  
pp. 1689-1693 ◽  
Author(s):  
Rongtao Zhu ◽  
Yipu Zhao ◽  
Xiaobo Li ◽  
Tao Bai ◽  
Shuai Wang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Penehyclidine Hydrochloride

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.

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

2012 ◽  
Vol 112 (7) ◽  
pp. 1184-1190 ◽  
Author(s):  
Carlos Fernando Ronchi ◽  
Jose Roberto Fioretto ◽  
Ana Lucia Anjos Ferreira ◽  
Carolina Bragiola Berchieri-Ronchi ◽  
Camila Renata Correa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mechanical Ventilation ◽  
Dna Damage ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Comet Assay ◽  
Lung Tissue ◽  
Significant Positive Correlation ◽  
Target Tissue ◽  
Total Antioxidant

Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38°C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation ( r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation ( r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage ( r = −0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans.

scholarly journals Pathophysiological aspects of severe acute pancreatitis-associated lung injury

2005 ◽  
Vol 133 (1-2) ◽  
pp. 76-81 ◽  
Author(s):  
Maja Surbatovic ◽  
Krsta Jovanovic ◽  
Sonja Radakovic ◽  
Nikola Filipovic
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Mortality Rate ◽  
Lung Injury ◽  
Severe Acute Pancreatitis ◽  
Distress Syndrome ◽  
Severe Form ◽  
Very High ◽  
Intensive Medicine

Acute pancreatitis is an inflammatory process which occurs in severe form in 20% of all patients, out of whom 1596-25% will die. The incidence of severe acute pancreatitis-associated lung injury (APALI) varies from 15% to 55% and its severity varies from mild hypoxemia to acute respiratory distress syndrome (ARDS). Acute lung injury (ALI) and ARDS are the most significant manifestations of extra abdominal dysfunctions in severe acute pancreatitis with mortality rate as high as 60% in the first week of the onset of illness. Different pathophysiological mechanisms of severe acute pancreatitis-associated lung injury have been described. The role of enzymes, adhesion molecules, neutrophils, fibronectin and various inflammatory mediators has been emphasized. Mechanism of the acute lung injury associated with the acute pancreatitis is very complex and has not been clear yet. There is no specific therapeutic procedure and mortality rate is very high. Therefore, further studies are necessary to address this acute and growing problem in intensive medicine.

scholarly journals c-Fos is a mechanosensor that regulates inflammatory responses and lung barrier dysfunction during ventilator-induced acute lung injury

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Leilei Zhou ◽  
Chunju Xue ◽  
Zongyu Chen ◽  
Wenqing Jiang ◽  
Shuang He ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protein Expression ◽  
Tidal Volume ◽  
Lung Tissue ◽  
Inflammatory Reaction ◽  
Specific Inhibitor ◽  
Control Group ◽  
Fos Protein ◽  
Volume Group

Abstract Background As one of the basic treatments performed in the intensive care unit, mechanical ventilation can cause ventilator-induced acute lung injury (VILI). The typical features of VILI are an uncontrolled inflammatory response and impaired lung barrier function; however, its pathogenesis is not fully understood, and c-Fos protein is activated under mechanical stress. c-Fos/activating protein-1 (AP-1) plays a role by binding to AP-1 within the promoter region, which promotes inflammation and apoptosis. T-5224 is a specific inhibitor of c-Fos/AP-1, that controls the gene expression of many proinflammatory cytokines. This study investigated whether T-5224 attenuates VILI in rats by inhibiting inflammation and apoptosis. Methods The SD rats were divided into six groups: a control group, low tidal volume group, high tidal volume group, DMSO group, T-5224 group (low concentration), and T-5224 group (high concentration). After 3 h, the pathological damage, c-Fos protein expression, inflammatory reaction and apoptosis degree of lung tissue in each group were detected. Results c-Fos protein expression was increased within the lung tissue of VILI rats, and the pathological damage degree, inflammatory reaction and apoptosis in the lung tissue of VILI rats were significantly increased; T-5224 inhibited c-Fos protein expression in lung tissues, and T-5224 inhibit the inflammatory reaction and apoptosis of lung tissue by regulating the Fas/Fasl pathway. Conclusions c-Fos is a regulatory factor during ventilator-induced acute lung injury, and the inhibition of its expression has a protective effect. Which is associated with the antiinflammatory and antiapoptotic effects of T-5224.

Sign in / Sign up

Export Citation Format

Share Document