scholarly journals Comparison of direct and indirect models of early induced acute lung injury

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Laura Chimenti ◽  
Luis Morales-Quinteros ◽  
Ferranda Puig ◽  
Marta Camprubi-Rimblas ◽  
Raquel Guillamat-Prats ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Acute Phase ◽  
Cecal Ligation ◽  
Sprague Dawley ◽  
Acid Aspiration ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Gastric Contents ◽  
Bacterial Superinfection

Abstract Background The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS. Aim To compare different experimental animal models of ALI, based on direct or indirect mechanisms of lung injury, to characterize a model which more closely could reproduce the acute phase of human ARDS. Materials and methods Adult male Sprague-Dawley rats were subjected to intratracheal instillations of (1) HCl to mimic aspiration of gastric contents; (2) lipopolysaccharide (LPS) to mimic bacterial infection; (3) HCl followed by LPS to mimic aspiration of gastric contents with bacterial superinfection; or (4) cecal ligation and puncture (CLP) to induce peritonitis and mimic sepsis. Rats were sacrificed 24 h after instillations or 24 h after CLP. Results At 24 h, rats instilled with LPS or HCl-LPS had increased lung permeability, alveolar neutrophilic recruitment and inflammatory markers (GRO/KC, TNF-α, MCP-1, IL-1β, IL-6). Rats receiving only HCl or subjected to CLP had no evidence of lung injury. Conclusions Rat models of ALI induced directly by LPS or HCl-LPS more closely reproduced the acute phase of human ARDS than the CLP model of indirectly induced ALI.

scholarly journals Activation of cholinergic anti-inflammatory pathway involved in therapeutic actions of α-mangostin on lipopolysaccharide-induced acute lung injury in rats

2020 ◽  
Vol 34 ◽  
pp. 205873842095494
Author(s):  
Zhe Yang ◽  
Qin Yin ◽  
Opeyemi Joshua Olatunji ◽  
Yan Li ◽  
Shu Pan ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Sprague Dawley ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Inflammatory Pathway ◽  
Inflammatory Reactions ◽  
Sprague Dawley Rats ◽  
Anti Inflammatory

Introduction: Alpha-mangostin (MAN) possesses a wide variety of pharmacological effects. In this study, we investigated its effect on cholinergic anti-inflammatory pathway (CAP), and tested if CAP regulation was involved in the therapeutic action on acute lung injury (ALI). Methods: Male Sprague Dawley rats were pre-treated with MAN (40 mg/kg) for 3 days and ALI was induced with an intraperitoneal injection of lipopolysaccharide (LPS). Certain rats received monolateral vagotomy or sham surgery. The effects on inflammatory reactions and relevant pathways in ALI rats or LPS pre-treated RAW 264.7 cells were investigated by histological, immunohistochemical, immunoblotting, RT-qPCR, and immunofluorescence assays, while levels of proinflammatory cytokines, acetylcholine (Ach) and the enzymatic activity of acetylcholinesterase (AchE) were determined by corresponding quantitative kits. Results: Oral administration of MAN reduced the severity of ALI, while vagotomy surgery antagonized this effect. MAN restored the decline in α7 nicotinic acetylcholine receptor (α7nAchR) in the lungs of ALI rats, and promoted the expression of α7nAchR and choline acetyltransferase (CHAT) in RAW 264.7 cells. Although AchE expression was barely affected by MAN at 5 μg/ml, its catalytic activity was reduced by almost 95%. Extracellular rather than intracellular Ach was notably raised shortly after MAN treatment. Furthermore, MAN at 5 μg/ml effectively inhibited LPS-induced increase in phosphorylation and nucleus translocation of p65 subunit, and secretion of TNF-α and IL-1β, which was then offset by methyllycaconitine citrate hydrate. Conclusion: MAN activated CAP by increasing peripheral Ach and up-regulating α7nAchR expression, which eventually led to NF-κB inhibition and remission of acute inflammations.

High-volume ventilation induces pentraxin 3 expression in multiple acute lung injury models in rats

2007 ◽  
Vol 292 (1) ◽  
pp. L144-L153 ◽  
Author(s):  
Daisuke Okutani ◽  
Bing Han ◽  
Marco Mura ◽  
Thomas K. Waddell ◽  
Shaf Keshavjee ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
High Volume ◽  
Pentraxin 3 ◽  
Sprague Dawley ◽  
Ventilator Induced Lung Injury ◽  
Sprague Dawley Rats ◽  
Volume Ventilation ◽  
Highly Correlated ◽  
Injury Models

Pentraxin 3 (PTX3) is an acute-phase protein, which can be produced by a variety of tissue cells at the site of infection or inflammation. It plays an important role in innate immunity in the lung and in mediating acute lung injury. The aim of this study was to determine the effect of mechanical ventilation on PTX3 expression in multiple lung injury models. Male Sprague-Dawley rats were challenged with intravenous injection of lipopolysaccharide (LPS) or hemorrhage followed by resuscitation (HS). The animals were then subjected to either relatively higher (12 ml/kg) or lower (6 ml/kg, positive end-expiratory pressure of 5 cmH2O) volume ventilation for 4 h. High-volume ventilation significantly enhanced PTX3 expression in the lung, either alone or in combination with LPS or hemorrhage. A significant increase of PTX3 immunohistochemistry staining in the lung was seen in all injury groups. The PTX3 expression was highly correlated with the severity of lung injury determined by blood gas, lung elastance, and wet-to-dry ratio. To determine the effects of HS, LPS, or injurious ventilation (25 ml/kg) alone on PTX3 expression, another group of rats was studied. Injurious ventilation significantly damaged the lung and increased PTX3 expression. A local expression of PTX3 induced by high-volume ventilation, either alone or in combination with other pathological conditions, suggests that it may be an important mediator in ventilator-induced lung injury.

scholarly journals Differential Effects of Buffered Hypercapnia versus  Hypercapnic Acidosis on Shock and Lung Injury Induced by Systemic Sepsis

2009 ◽  
Vol 111 (6) ◽  
pp. 1317-1326 ◽  
Author(s):  
Brendan D. Higgins ◽  
Joseph Costello ◽  
Maya Contreras ◽  
Patrick Hassett ◽  
Daniel O' Toole ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Lung Injury ◽  
Cecal Ligation ◽  
Hypercapnic Acidosis ◽  
Cecal Ligation And Puncture ◽  
Sprague Dawley ◽  
Systemic Sepsis ◽  
Sprague Dawley Rats ◽  
Hemodynamic Deterioration ◽  
Hemodynamic Profile

Background Acute hypercapnic acidosis protects against lung injury caused by nonseptic insults and after both pulmonary and systemic sepsis. The authors wished to dissect the contribution of the acidosis versus hypercapnia per se to the effects of hypercapnic acidosis on the hemodynamic profile and severity of lung injury induced by systemic sepsis. Methods In the hypercapnic acidosis series, adult male Sprague-Dawley rats were randomized to normocapnia or hypercapnic acidosis-produced by adding 5% carbon dioxide to the inspired gas-and cecal ligation and puncture performed. In the buffered hypercapnia series, animals were first randomized to housing under conditions of environmental normocapnia or hypercapnia-produced by exposure to 8% carbon dioxide-to allow renal buffering. After 96 h, cecal ligation and puncture was performed. In both series, the animals were ventilated for 6 h, and the severity of the lung injury and hemodynamic deterioration were assessed. Results Both hypercapnic acidosis and buffered hypercapnia attenuated the development and severity of hypotension and reduced lactate accumulation compared to normocapnia. Hypercapnic acidosis reduced lung injury and inflammation, decreased mean (+ or - SD) bronchoalveolar lavage protein concentration (232 + or - 50 versus 279 + or - 27 microg x ml(-1)) and median neutrophil counts (3,370 versus 9,120 cells x ml(-1)), and reduced histologic lung injury. In contrast, buffered hypercapnia did not reduce the severity of systemic sepsis induced lung injury. Conclusions Both hypercapnic acidosis and buffered hypercapnia attenuate the hemodynamic consequences of systemic sepsis. In contrast, hypercapnic acidosis, but not buffered hypercapnia, reduced the severity of sepsis-induced lung injury.

scholarly journals Angelica Polysaccharide Ameliorates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 and NF-κB Signaling Pathways in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yan Zhu ◽  
Taocheng Meng ◽  
Aichen Sun ◽  
Jintao Li ◽  
Jinlai Li
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathways ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
Receptor Protein ◽  
Lung Edema ◽  
Caspase 1 ◽  
Tnf Α

Objective. This study aimed to explore the role of angelica polysaccharide (AP) in sepsis-induced acute lung injury (ALI) and its underlying molecular mechanism. Methods. A sepsis model of cecal ligation and puncture (CLP) in male BALB/C mice was used. Then, 24 h after CLP, histopathological changes in lung tissue, lung wet/dry weight ratio, and inflammatory cell infiltration were analyzed. Next, levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18), as well as the activity of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH), were measured to assess the role of AP. The protein expression of NF-κB p65, p-NF-κB p65, IκBα, p-IκBα, nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3), ASC, and caspase-1 was detected by western blot. In addition, the expression of p-NF-κB p65 and NLRP3 was detected by immunohistochemistry. Results. AP treatment ameliorated CLP-induced lung injury and lung edema, as well as decreased the number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF). AP reduced the levels of TNF-α, IL-1β, IL-6, and IL-18 in BALF, as well as in serum. Moreover, AP decreased MPO activity and MDA content, whereas increased SOD and GSH levels. AP inhibited the expression of p-NF-κB p65, p-IκBα, NLRP3, ASC, and caspase-1, while promoted IκBα expression. Conclusion. This study demonstrated that AP exhibits protective effects against sepsis-induced ALI by inhibiting NLRP3 and NF-κB signaling pathways in mice.

scholarly journals miR-20a attenuates acute lung injury in septic rats via targeting TLR4

2021 ◽  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Tissue ◽  
Cecal Ligation ◽  
Normal Group ◽  
Lung Damage ◽  
Luciferase Reporter ◽  
Arterial Bleeding ◽  
Tnf Α

Background: Sepsis is most likely to cause lung damage in patients, and the detection rate and mortality rate are high. Here, we investigated the expression of miR-20a in sepsis-induced acute lung injury (ALI) rats and its effect on inflammatory response, and reveal its possible molecular mechanism. Method: The model of acute lung injury caused by sepsis in rats was established by cecal ligation and puncture. The expression of miR-20a in lung tissue was determined by RT-qPCR. Acute lung injury rats were injected with 5 nmol miR-20a agomir or agomir NC every day for 3 days. Rats were sacrificed by arterial bleeding and lung tissues were removed. Serum interleukin (IL) -1β, IL-6, and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE staining was used to observe the pathology of lung tissue and calculate the pathological score of lung injury. Western blot to determine the level of TLR4 and nuclear transcription factor κB p65 (NF-κB p65) protein in lung tissue. The luciferase reporter assay was used to verify the binding effect of miR-20a on the 3 non-coding TLR4. Results: We found that compared with that in Normal group, the expression of miR-20a in lung tissues of rats with ALI was decreased (p < 0.05). In miR-20a agomir group, the plasma level of IL-1β, IL-6, and TNF-α was significantly lower than that in agomir NC group and ALI group (p < 0.05), while higher than those in Normal group (p < 0.05). The HE staining results showed that the pathological score of lung injury in rats in miR-20a agomir group was lower than that of agomir NC group and ALI group (p < 0.05). Compared with agomir NC group and ALI group, the expression of TLR4 and NF-κB p65 in miR-20a agomir group was decreased (p < 0.01). The luciferase reporting experiment confirmed that TLR4 was a target gene of miR-20a. Conclusion: To sum up, miR-20a exerts a protective effect on sepsis-induced ALI rats through its anti-inflammatory effect. The targeting of TLR4 by miR-20a may be an effective method to reduce the inflammatory response in sepsis-induced ALI.

scholarly journals Anti-Inflammatory and Anticoagulative Effects of Paeonol on LPS-Induced Acute Lung Injury in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Pin-Kuei Fu ◽  
Chieh-Liang Wu ◽  
Tung-Hu Tsai ◽  
Ching-Liang Hsieh
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Interleukin 1 ◽  
Intraperitoneal Administration ◽  
Lavage Fluid ◽  
Polymorphonuclear Neutrophils ◽  
Sprague Dawley ◽  
Intratracheal Administration ◽  
Sprague Dawley Rats ◽  
Anti Inflammatory

Paeonol is an active component of Moutan Cortex Radicis and is widely used as an analgesic, antipyretic, and anti-inflammatory agent in traditional Chinese medicine. We wanted to determine the role of paeonol in treating adult respiratory distress syndrome (ARDS). We established an acute lung injury (ALI) model in Sprague-Dawley rats, which was similar to ARDS in humans, using intratracheal administration of lipopolysaccharide (LPS). The intraperitoneal administration of paeonol successfully reduced histopathological scores and attenuated myeloperoxidase-reactive cells as an index of polymorphonuclear neutrophils infiltration and also reduces inducible nitric oxide synthase expression in the lung tissue, at 16 h after LPS administration. In addition, paeonol reduced proinflammatory cytokines in bronchoalveolar lavage fluid, including tumor-necrosis factor-α, interleukin-1β, interleukin-6, and plasminogen-activated inhibition factor-1. These results indicated that paeonol successfully attenuates inflammatory and coagulation reactions to protect against ALI.

scholarly journals Increased effort during partial ventilatory support is not associated with lung damage in experimental acute lung injury

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Dietrich Henzler ◽  
Alf Schmidt ◽  
Zhaolin Xu ◽  
Nada Ismaiel ◽  
Haibo Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pressure Support ◽  
Diffuse Alveolar Damage ◽  
Ventilatory Support ◽  
Lung Damage ◽  
Respiratory Effort ◽  
Sprague Dawley ◽  
Mechanical Pressure ◽  
Acid Aspiration

Abstract Background An on-going debate exists as to whether partial ventilatory support is lung protective in an acute phase of ARDS. So far, the effects of different respiratory efforts on the development of ventilator-associated lung injury (VALI) have been poorly understood. To test the hypothesis whether respiratory effort itself promotes VALI, acute lung injury (ALI) was induced in 48 Sprague Dawley rats by hydrochloric acid aspiration model. Hemodynamics, gas-exchange, and respiratory mechanics were measured after 4 h of ventilation in pressure control (PC), assist-control (AC), or pressure support with 100% (PS100), 60% (PS60), or 20% (PS20) of the driving pressure during PC. VALI was assessed by histological analysis and biological markers. Results ALI was characterized by a decrease in PaO2/FiO2 from 447 ± 75 to 235 ± 90 mmHg (p < 0.001) and dynamic respiratory compliance from 0.53 ± 0.2 to 0.28 ± 0.1 ml/cmH2O (p < 0.001). There were no differences in hemodynamics or respiratory function among groups at baseline or after 4 h of ventilation. The reduction of mechanical pressure support was associated with a compensatory increase in an inspiratory effort such that peak inspiratory transpulmonary pressures were equal in all groups. The diffuse alveolar damage score showed significant lung injury but was similar among groups. Pro- and anti-inflammatory proteins in the bronchial fluid were comparable among groups. Conclusions In experimental ALI in rodents, the respiratory effort was increased by reducing the pressure support during partial ventilatory support. In the presence of a constant peak inspiratory transpulmonary pressure, an increased respiratory effort was not associated with worsening ventilator-associated lung injury measured by histologic score and biologic markers.

scholarly journals Effect of rapamycin on early stage apoptosis of neutrophils in Sprague-Dawley rats with acute lung injury

2017 ◽  
Vol 7 (2) ◽  
pp. 148-152
Author(s):  
Liwei Li ◽  
Changtai Zhu ◽  
Ye Yuan ◽  
Zhiqiang Li
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Early Stage ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Remote Inflammatory Preconditioning Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Intrinsic Apoptosis in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yong Liu ◽  
Jiahang Xu ◽  
Liang Zhao ◽  
Jing Cheng ◽  
Baojun Chen
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Animal Experiments ◽  
Intrinsic Apoptosis ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Lung Protection ◽  
Sprague Dawley Rats ◽  
The Right

Background. Acute lung injury (ALI) always leads to severe inflammation. As inflammation and oxidative stress are the common pathological basis of endotoxin-induced inflammatory injury and ischemic reperfusion injury (IRI), we speculate that remote ischemic preconditioning (RIPC) can be protective for ALI when used as remote inflammatory preconditioning (RInPC). Method. A total of 21 Sprague-Dawley rats were used for the animal experiments. Eighteen rats were equally and randomly divided into the control (NS injection), LPS (LPS injection), and RInPC groups. The RInPC was performed prior to the LPS injection via tourniquet blockage of blood flow to the right hind limb and adopted three cycles of 5 min tying followed by 5 min untying. Animals were sacrificed 24 hours later. There were 2 rats in the LPS group and 1 in the RInPC group who died before the end of the experiment. Supplementary experiments in the LPS and RInPC groups were conducted to ensure that 6 animals in each group reached the end of the experiment. Results. In the present study, we demonstrated that the RInPC significantly attenuated the LPS-induced ALI in rats. Apoptotic cells were reduced significantly by the RInPC, with the simultaneous improvement of apoptosis-related proteins. Reduction of MPO and MDA and increasing of SOD activity were found significantly improved by the RInPC. Increasing of TNF-α, IL-1β, and IL-6 induced by the LPS was inhibited, while IL-10 was significantly increased by RInPC, compared to the LPS group. Conclusion. RInPC could inhibit inflammation and attenuate oxidative stress, thereby reducing intrinsic apoptosis and providing lung protection in the LPS-induced ALI in rats.

scholarly journals MEF2C alleviates acute lung injury in cecal ligation and puncture (CLP)-induced sepsis rats by up-regulating AQP1

2021 ◽  
Vol 49 (5) ◽  
pp. 117-124
Author(s):  
Wenmei Liang ◽  
Li Guo ◽  
Tonghua Liu ◽  
Song Qin
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Tunel Staining ◽  
Cecal Ligation And Puncture ◽  
Tnf Α ◽  
Factor Α

Background: Sepsis is a systemic inflammatory response syndrome and leads to patient’s death. Objective: To investigate the effect of myocyte enhancer factor 2 (MEF2C) on acute lung injury (ALI) with sepsis and its possible mechanism.Material and Methods: The cecal ligation and puncture (CLP)-induced sepsis rat model was established. The lung injury was determined by lung wet–dry weight ratio, the concentration of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), Interlukin (IL)-6, IL-1β, and IL-10, were measured by the enzyme-linked-immunosorbent serologic assay kit. The cell apoptosis was detected by TUNEL staining assay.Results: Interestingly, MEF2C was down-regulated in this model. Moreover, adeno-associated virus (AAV)-MEF2C treatment markedly suppressed TNF-α, IL-1β, and IL-6 concentrations but promoted IL-10 concentration in serum in CLP-challenged rats. Besides, overexpression of MEF2C alleviates CLP-induced lung injury. Interestingly, AAV-MEF2C treatment was confirmed to suppress apoptosis in CLP-induced sepsis rats as well as promote aquaporin APQ1 expres-sion. Mechanistically, the rescue experiments indicated that MEF2C alleviated CLP-induced lung inflammatory response and apoptosis via up-regulating AQP1.Conclusion: In summary, overexpression of MEF2C suppressed CLP-induced lung inflamma-tory response and apoptosis via up-regulating AQP1, providing a novel therapeutic target for sepsis-induced ALI.

Sign in / Sign up

Export Citation Format

Share Document