scholarly journals GPA Peptide Attenuates Sepsis-Induced Acute Lung Injury in Mice via Inhibiting Oxidative Stress and Pyroptosis of Alveolar Macrophage

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yukun Liu ◽  
Yongsheng Zhang ◽  
Quanrui Feng ◽  
Qinxin Liu ◽  
Jie Xie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophage ◽  
Inflammatory Cell ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Cecal Ligation ◽  
Regulatory Function ◽  
Protective Effects

Acute lung injury (ALI) has been known to be a devastating form of respiratory infection and an important contributor to mortality in intensive care, due to its lacking of effective treatment. Inflammation, oxidative stress, and pyroptosis are associated with multiple kinds of inflammatory diseases such as ALI. It is commonly accepted that Gly-Pro-Ala (GPA) peptide regulates oxidative stress and pyroptosis in different kinds of inflammatory diseases. Our study is aimed at exploring the regulatory function and protective effects of GPA peptides on ALI. In the current study, the cecal ligation and puncture (CLP) technique was used to evoke sepsis in mice, and GPA peptide was administered intraperitoneally with different concentrations (50, 100, and 150 mg/kg) after CLP. Histopathological changes and the ratio of wet-to-dry in lung were recorded and analyzed. We also investigated the level of oxidative stress, inflammation, and pyroptosis. Results showed that GPA peptide significantly ameliorated CLP-stimulated lung tissue injury, impeded proinflammatory cytokine release, and reduced inflammatory cell infiltration. Additionally, GPA peptide suppressed oxidative stress and caspase-1-dependent pyroptosis in alveolar macrophages. Furthermore, our study showed that the GPA peptide prevents alveolar macrophage from undergoing pyroptosis by attenuating ROS. In conclusion, results demonstrated that GPA peptide has protective effects in CLP-stimulated ALI by inhibiting oxidative stress as well as pyroptosis of alveolar macrophage.

scholarly journals Down-regulation of SNHG16 alleviates the acute lung injury in sepsis rats through miR-128-3p/HMGB3 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Junli Sun ◽  
Keke Xin ◽  
Chenghui Leng ◽  
Jianlin Ge
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Western Blot ◽  
Cell Viability ◽  
Inflammatory Diseases ◽  
Cecal Ligation ◽  
Inflammatory Factors ◽  
Lung Epithelial

Abstract Background Long noncoding RNAs contribute to various inflammatory diseases, including sepsis. We explore the role of small nucleolar RNA host gene 16 (SNHG16) in sepsis-mediated acute lung injury (ALI) and inflammation. Methods A sepsis-induced ALI rat model was constructed by the cecal ligation and perforation method. The profiles of SNHG16, miR-128-3p, and high-mobility group box 3 (HMGB3) were monitored by quantitative reverse transcription PCR and Western blot. The pathologic changes of lung tissues were evaluated by Hematoxylin–Eosin staining, immunohistochemistry, and dry and wet method. Meanwhile, the pro-inflammatory factors and proteins were determined by ELISA and Western blot. In contrast, a sepsis model in BEAS-2B was induced with lipopolysaccharide (LPS) to verify the effects of SNHG16/miR-128-3p/HMGB3 on lung epithelial cell viability and apoptosis. Results As a result, SNHG16 and HMGB3 were up-regulated, while miR-128-3p was down-regulated in sepsis-induced ALI both in vivo and in vitro. Inhibiting SNHG16 reduced the apoptosis and inflammation in the sepsis-induced ALI model. Overexpressing SNHG16 promoted LPS-mediated lung epithelial apoptosis and inhibited cell viability and inflammation, while miR-128-3p had the opposite effects. Mechanistically, SNHG16 targeted miR-128-3p and attenuated its expression, while miR-128-3p targeted the 3′ untranslated region of HMGB3. Conclusions Overall, down-regulating SNHG16 alleviated the sepsis-mediated ALI by regulating miR-128-3p/HMGB3.

scholarly journals MiR-574-5p alleviates sepsis-induced acute lung injury by regulating TRAF6/NF-κB pathway

2020 ◽  
Vol 19 (4) ◽  
pp. 676-682
Author(s):  
Changfu Xu ◽  
Lei Chong ◽  
Gang Yu ◽  
Hailin Zhang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cell ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Cytokine Expression ◽  
Inflammatory Cell Infiltration ◽  
Luciferase Assay ◽  
Cell Infiltration ◽  
Mice Model

Purpose: To investigate the protective effect of miR-574-5p pretreatment against acute lung injury (ALI) induced by sepsis.Methods: A male C57BL/6 mouse model of sepsis-induced ALI was established by cecal ligation and puncture (CLP) and treated with miR-574-5p agomir (intravenous injection, 80 mg/kg per day, 3 days). After that, blood and lung samples were obtained for histopathological observation. Myeloperoxidase (MPO) activity, inflammatory cell infiltration, and cytokine expression were analyzed. The target gene of miR-574-5p was predicted using TargetScan prediction, and verified by luciferase assay and western blot.Results: In sepsis-induced ALI mice model, downregulation of miR-574-5p was observed. Pretreatment of miR-574-5p significantly alleviated ALI by suppressing histological damage, and reducing MPO activity and inflammatory cell infiltration, as well as decreasing cytokine expression. The  underlying mechanism was that miR-574-5p targeted TNF receptor associated factor 6 (TRAF6) and suppressed the downstream NF-κB pathway. Moreover, TRAF6 overexpression reversed the effects of miR-574-5p on ALI.Conclusion: MiR-574-5p pretreatment suppresses inflammatory responses, thus reducing lung injury induced by sepsis in mice, partly via the regulation of TRAF6 and NF-κB pathway. Therefore, this approach can potentially be used for the clinical management of ALI in humans Keywords: Sepsis, Acute lung injury, MiR-574-5p, TRAF6, NF-κB pathway

Isoacteoside Attenuates Septic Acute Lung Injury by Inhibiting Inflammation, Oxidative Stress and Endothelial Hyperpermeability in Mice

2021 ◽  
Author(s):  
Yan-nian Luo ◽  
Nan-nan He ◽  
Juan Xu ◽  
Rui Wang ◽  
Wen Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Survival Rate ◽  
Lung Injury ◽  
Cecal Ligation ◽  
Endothelial Permeability ◽  
Mouse Serum ◽  
Control Group ◽  
Expression Levels ◽  
Endothelial Hyperpermeability

Abstract The present study was aimed to explore the protective role of isoacteoside (ISO) in cecal ligation and puncture (CLP)-induced acute lung injury (ALI) in mice. Mice were divided into the following groups: sham control group, ALI group, and ALI+ISO group, in which mice received 10,50 or 100 mg/kg/day of ISO for 3 days before, 0h and 12h after CLP surgery. In the first experiment, all mice were maintained until 72 h after the CLP operation to calculate the survival rate. In the second experiment, mouse serum and lung and bronchoalveolar lavage fluid (BALF) were collected 24 h after model establishment for detection. The results revealed that ISO significantly improved the ALI associated survival rate, reduced the pathological injury, ALI score, infiltration of inflammatory cells, leakage of cells and proteins into BALF, systemic and local cytokine secretion, and pulmonary oxidative stress. Moreover, ISO significantly inhibited the expression levels of the pro-inflammatory proteins TLR4, MyD88, p-NF-κB p65, p-IKKαβ, and p-IκBα and increased the expression levels of the endothelial permeability related proteins ZO-1, claudin 5 and VE-cadherin. In conclusions, ISO mitigated acute lung injury in mice which was attributed to the capacity of ISO to inhibit inflammation, oxidative stress and endothelial hyperpermeability.

scholarly journals Amentoflavone prevents sepsis-associated acute lung injury through Nrf2-GCLc-mediated upregulation of glutathione

2016 ◽  
Vol 64 (1) ◽  
Author(s):  
Yuan Zong ◽  
Huali Zhang
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Medical Problem ◽  
Binding Activity ◽  
Content Increase ◽  
Protective Effects ◽  
Sod Activity ◽  
Buthionine Sulphoximine

Sepsis is a serious medical problem that is one of the main causes of high mortality in intensive care units. Fifty percent of patients with severe sepsis will develop acute lung injury (ALI). Amentoflavone (AMF) is a polyphenolic compound possessing potent anti-inflammatory activities. The present study was designed to explore the protective effects of AMF against ALI in CLP-induced septic rats. The results showed that AMF administration protected against septic ALI, as reflected by marked amelioration of histological injury of lung tissues and decrease of pulmonary edema in CLP-treated rats. AMF ameliorated CLP-induced increase of systemic and lung TNF-α and IL-1β and the binding activity of p65 NF-κB, indicating the inhibition of inflammation induced by CLP. Moreover, AMF prevented CLP-induced oxidative stress, as evidenced by increase of oxygen consumption rate, decrease of TBARS content, increase of SOD activity and GSH level in lung tissue of CLP-treated rats. CLP resulted in significant decrease of mRNA expression of Nrf2 and GCLc, which was inhibited by AMF. AMF-induced protective effects on ALI, inflammation, and oxidative stress were inhibited by lentivirus-mediated shRNA of Nrf2 and buthionine sulphoximine (BSO), an inhibitor of GSH synthesis. AMF increased Nrf2-binding activity with GCLc promoters in lung tissue of CLP-treated rats. The results suggested that AMF protected against ALI in septic rats through upregulation of Nrf2-GCLc signaling, enhancement of GSH antioxidant defense, reduction of oxidative stress and final amelioration of inflammation and histological injury of lung. The data provide new therapeutic options for the treatment of sepsis-associated ALI.

scholarly journals UHPLC-Q-TOF MS-Based Metabolic Analysis for the Therapeutic Efficacy of “Xuebijing Injection” against Sepsis-Induced Acute Lung Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Xuan Shi ◽  
Guannan Chen ◽  
Juan Wei ◽  
Di Feng ◽  
Yuanli Chen ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Metabolic Pathway ◽  
Therapeutic Efficacy ◽  
Cecal Ligation ◽  
Sepsis Group ◽  
Sham Operation ◽  
Protective Effects ◽  
Xuebijing Injection ◽  
Tof Ms

“Xuebijing Injection” (XBJ) is a traditional Chinese medicine and has been wildly used in the treatment of sepsis in China. However, few studies have reported the use of XBJ in sepsis with acute lung injury (ALI). This study aimed to investigate the therapeutic efficacy of XBJ against sepsis-induced ALI. Generally a total of 27 mice were equally randomized into three groups: a sham group was given saline before sham operation. A sepsis group received the cecal ligation and puncture (CLP) operation only. A sepsis+XBJ group, XBJ, was injected at 72, 48, and 24 h before CLP operation. The lung tissue was collected for UHPLC-Q-TOF/MS profiling analysis, biomarker identification, and pathway analysis. With the analysis of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), forty-five purine, amino acid, and sphingolipid metabolites in lung tissues were identified as potential biomarkers of sepsis-induced ALI, among which 22 were reversed in the sepsis+XBJ group significantly. Conclusively, our results suggest that purine metabolic pathway, glutathione metabolic pathway, sphingomyelin metabolic pathway, arachidonic acid metabolic pathway, and phospholipid metabolic pathway may be the potential therapeutic pathways to overcome sepsis-induced acute lung injury and we provided the potential mechanisms of protective effects of XBJ against ALI.

scholarly journals Inhibition of ERRα Aggravates Sepsis-Induced Acute Lung Injury in Rats via Provoking Inflammation and Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Wenfang Xia ◽  
Zhou Pan ◽  
Huanming Zhang ◽  
Qingshan Zhou ◽  
Yu Liu
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Cecal Ligation ◽  
Endothelial Permeability ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
Junction Protein ◽  
And Oxidative Stress

Inflammation and oxidative stress are critical pathologies that contribute to sepsis-induced acute lung injury (ALI). This study investigated the regulatory role of estrogen-related receptor alpha (ERRα) in an experimental model of sepsis-induced ALI. In vivo, a cecal ligation and puncture- (CLP-) induced ALI model was established in anesthetized rats. Animals were then randomly assigned to receive an intraperitoneal injection of vehicle or ERRα inverse agonist (XCT-790, 2.5 mg/kg). Administration of XCT-790 significantly aggravated a sepsis-induced increase in pathological damage of lung tissues, lung endothelial permeability, myeloperoxidase (MPO) activity in lung tissues, production of serum inflammatory factors, and inflammatory cell accumulation in bronchoalveolar lavage fluid. In addition, XCT-790 treatment exacerbated a CLP-induced decrease in lung superoxide dismutase and an increase in lung malondialdehyde levels. In vitro, the exposure of rat pulmonary microvascular endothelial cells (PMVECs) to lipopolysaccharide (LPS) resulted in increased endothelial permeability and reduced expression of tight junction protein ZO-1, Occludin, JAM-A, and adherens junction protein VE-cadherin, which were further deteriorated by knockdown of ERRα. In addition, LPS-triggered inflammatory factor production and increase in the expression of phosphorylated IκBα and NF-κB p65 were also exacerbated by silencing ERRα gene. Meanwhile, knockdown of ERRα dramatically promoted LPS-activated mitochondrial reactive oxygen species production and LPS-induced downregulation of Sirt3 protein levels in rat PMVECs. Taken together, our present study provides evidences that ERRα functions as a novel negative modulator of sepsis-induced ALI in rats. The underlying mechanisms responsible for ERRα-elicited effects are largely dependent on the regulation of inflammatory response and oxidative stress.

scholarly journals β-Nitrostyrene derivatives attenuate LPS-mediated acute lung injury via the inhibition of neutrophil-platelet interactions and NET release

2018 ◽  
Vol 314 (4) ◽  
pp. L654-L669 ◽  
Author(s):  
Yao-Wen Chang ◽  
Ching-Ping Tseng ◽  
Chih-Hsun Lee ◽  
Tsong-Long Hwang ◽  
Yu-Li Chen ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Diseases ◽  
Treatment Strategies ◽  
Neutrophil Function ◽  
Neutrophil Extracellular Trap ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Neutrophil Accumulation ◽  
Net Release

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are high-mortality and life-threatening diseases that are associated with neutrophil activation and accumulation within lung tissue. Emerging evidence indicates that neutrophil-platelet aggregates (NPAs) at sites of injury increase acute inflammation and contribute to the development of ALI. Although numerous studies have increased our understanding of the pathophysiology of ALI, there is still a lack of innovative and useful treatments that reduce mortality, emphasizing that there is an urgent need for novel treatment strategies. In this study, a new series of small compounds of β-nitrostyrene derivatives (BNSDs) were synthesized, and their anti-inflammatory bioactivities on neutrophils and platelets were evaluated. The new small compound C7 modulates neutrophil function by inhibiting superoxide generation and elastase release. Compound C7 elicits protective effects on LPS-induced paw edema and acute lung injury via the inhibition of neutrophil accumulation, proinflammatory mediator release, platelet aggregation, myeloperoxidase activity, and neutrophil extracellular trap (NET) release. NET formation was identified as the bridge for the critical interactions between neutrophils and platelets by confocal microscopy and flow cytometry. This research provides new insights for elucidating the complicated regulation of neutrophils and platelets in ALI and sheds further light on future drug development strategies for ALI/ARDS and acute inflammatory diseases.

scholarly journals Tanreqing Inhibits LPS-Induced Acute Lung Injury In Vivo and In Vitro Through Downregulating STING Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-Qiong He ◽  
Can-Can Zhou ◽  
Jiu-Ling Deng ◽  
Liang Wang ◽  
Wan-Sheng Chen
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Lung Edema ◽  
Protective Effects ◽  
And Oxidative Stress

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1β, and IFN-β). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.

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