scholarly journals Pristimerin attenuates sepsis-induced lung injury by regulating nuclear factor kappaB/high-mobility group box 1 pathway

2020 ◽  
Vol 19 (6) ◽  
pp. 1167-1171
Author(s):  
Xiao Wang ◽  
Lei Huang ◽  
Peng Li
Keyword(s):  
Lung Injury ◽  
Lung Tissue ◽  
Inflammatory Mediators ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
High Mobility ◽  
Dry Weight ◽  
Serum Levels ◽  
High Mobility Group ◽  
Lung Injury Score

Purpose: To determine the effect of pristimerin on sepsis-induced lung injury, and the underlying mechanism of action.Methods: Lung injury was established in mice via induction of sepsis through cecal ligation and puncture (CLP). The effect of pristimerin was evaluated based on lung wet/dry weight and PaO2/FiO2 ratios. Lung tissue was subjected to immunohistochemical and histopathological analyses, as well as Western blotting. Furthermore, the serum levels of inflammatory mediators were determined.Results: Pristimerin reversed the altered lung wet/dry weight ratio and PaO2/FiO2 ratio in the lung, and also reduced lung injury score, relative to CLP group (p < 0.05). Moreover, it suppressed nucleocytoplasmic translocation of high mobility group protein B1 (HMGB1) in lung tissue. Serum levels of inflammatory mediators and expression levels of inducible nitric oxide synthase and nuclear factorkappaB p65 were significantly reduced by pristimerin (p < 0.05).Conclusion: Pristimerin ameliorates sepsis-induced lung injury by inhibiting HMGB1/NF-κB. Thus, this compound has a potential for clinical application in the management of lung injury. Keywords: Pristimerin, Sepsis, Lung injury, Inflammatory mediators, HMGB1

Attenuation of hyperoxic lung injury by the 21-aminosteroid U-74389G

1995 ◽  
Vol 78 (5) ◽  
pp. 1635-1641 ◽  
Author(s):  
S. Tasaka ◽  
A. Ishizaka ◽  
T. Urano ◽  
K. Sayama ◽  
F. Sakamaki ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Tissue ◽  
Guinea Pigs ◽  
Weight Ratio ◽  
Dry Weight ◽  
Endothelial Damage ◽  
Lung Water ◽  
Tissue Samples ◽  
Cell Accumulation ◽  
Hyperoxic Lung Injury

Hyperoxic lung injury is attributable to oxygen radicals produced under hyperoxic conditions. The 21-aminosteroid (AS), U-74389G, is a potent antioxidant. We examined the effect of U-74389G on lung injury in guinea pigs during exposure to 90% O2 for 48 h. We injected either vehicle or 10 mg/kg of U-74389G 30 min before the O2 exposure and injected the same dose 12, 24, and 36 h later. We performed two series of experiments after exposure. In the first series, we measured the clearance rate of 99mTc-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups consisting of 1) control (n = 6) O2 alone (n = 6), and 3) O2 + AS (n = 6). In the second series, pulmonary endothelial injury was estimated by using 28 guinea pigs divided into four experimental groups consisting of 1) control (n = 8), 2) AS alone (n = 5), 3) O2 alone (n = 6), and 4) O2 + AS (n = 9). In the second series, we measured the wet-to-dry weight ratio (W/D) as an index of lung water and the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) as indexes of pulmonary endothelial damage. Cell accumulation in BAL fluid and lung tissue samples was also assessed in the second series.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Lactate as a Potential Biomarker of Sepsis in a Rat Cecal Ligation and Puncture Model

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaozhu Zhai ◽  
Zhengfei Yang ◽  
Guanghui Zheng ◽  
Tao Yu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Troponin I ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
High Mobility ◽  
Dry Weight ◽  
Cecal Ligation And Puncture ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Potential Biomarker ◽  
Puncture Model

We attempted to investigate whether blood lactate is a useful biomarker for sepsis in a rat cecal ligation and puncture (CLP) model. Male Sprague-Dawley rats underwent approximately 75% cecum ligation and two punctures to induce high-grade sepsis. A lactate of 1.64 mmol/L (Youden score of 0.722) was selected as the best cutoff value to predict the onset of sepsis after CLP exposure; 46 of 50 rats who survived 24 hours after the CLP were divided into the L group (lactate < 1.64 mmol/L) and M group (lactate ≥ 1.64 mmol/L). In the M group, the animals had significantly higher murine sepsis scores and none survived 5 days post-CLP, and the rate of validated septic animals, serum procalcitonin, high mobility group box 1, blood urea nitrogen, alanine transaminase, cardiac troponin I, and the wet-to-dry weight ratio were significantly higher compared to the L group. Worsen PaO2/FiO2, microcirculations, and mean arterial pressure were observed in the M group. More severe damage in major organs was confirmed by histopathological scores in the M group compared with the L group. In conclusion, lactate ≥ 1.64 mmol/L might serve as a potential biomarker to identify the onset of sepsis in a rat CLP model.

scholarly journals miR-128-3p enhances the protective effect of dexmedetomidine on acute lung injury in septic mice by targeted inhibition of MAPK14

2020 ◽  
Author(s):  
Li Ding ◽  
Xiang Gao ◽  
Shenghui Yu ◽  
Liufang Sheng
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Weight Ratio ◽  
Dry Weight ◽  
Serum Levels ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Targeted Inhibition

Abstract Background: To investigate the role of miR-128-3p and MAPK14 in the dexmedetomidine treatment of acute lung injury in septic mice. Methods: SPF C57BL/6 mice were divided into 8 groups. The pathological changes and wet/dry weight ratio (W/D), PaO 2 , PaCO 2 , MDA, SOD and MPO levels in lung tissue and the serum levels of inflammation factors were observed. Dual luciferase reporter assay was used to detect the targeting relationship of miR-128-3p and MAPK14, and qPCR and WB were used to detect the expression of miR-128-3p and MAPK14. Results: Compared with the Normal group, other groups had lower MDA, MPO, inflammatory factors levels and the expression level of MAPK14, while the content of SOD and the expression level of miR-128-3p was significantly decreased (all p < 0.05). Compared with the Model group, the contents of MDA, MPO, inflammatory factors in the DEX group and miR-128-3p mimic group were significantly decreased, and the content SOD was significantly increased, however, opposite results were occurred in oe-MAPK14 group (all p < 0.05). Compared with the DEX group, all the indicators in miR-128-3p mimic+DEX group showed significant improvement (all p < 0.05). Compared with the miR-128-3p mimic group, all the indicators were deteriorated in the miR-128-3p mimic+oe-MAPK14 group (all p < 0.05). The combination of DEX and oe-MAPK14 blocked the protective effect of dexmedetomidine on acute lung injury in septic mice. Conclusion: miR-128-3p can further enhance the protective effect of dexmedetomidine on acute lung injury in septic mice by targeting and inhibiting MAPK14 expression.

scholarly journals Markedly Increased High-Mobility Group Box 1 Protein in a Patient with Small-for-Size Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Darren G. Craig ◽  
Patricia Lee ◽  
E. Anne Pryde ◽  
Ernest Hidalgo ◽  
Peter C. Hayes ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Fatal Case ◽  
High Mobility ◽  
Serum Levels ◽  
Normal Function ◽  
High Mobility Group ◽  
Hmgb1 Protein ◽  
Membrane Bound ◽  
Small For Size ◽  
Molecular Patterns

Background. Small-for-size syndrome (SFSS) occurs in the presence of insufficient liver mass to maintain normal function after liver transplantation. Murine mortality following 85% hepatectomy can be reduced by the use of soluble receptor for advanced glycation end products (sRAGE) to scavenge damage-associated molecular patterns and prevent their engagement with membrane-bound RAGE.Aims. To explore serum levels of sRAGE, high-mobility group box-1 (HMGB1) protein, and other soluble inflammatory mediators in a fatal case of SFSS.Methods. Serum levels of HMGB1, sRAGE, IL-18, and other inflammatory mediators were measured by ELISA in a case of SFSS, and the results were compared with 8 patients with paracetamol-induced acute liver failure (ALF) and 6 healthy controls (HC).Results. HMGB1 levels were markedly higher in the SFSS patient (92.1 ng/mL) compared with the ALF patients (median (IQR) 11.4 (3.7–14.8) ng/mL) and HC (1.42 (1.38–1.56) ng/mL). In contrast, sRAGE levels were lower in the SFSS patient (1.88 ng/mL) compared with the ALF patients (3.53 (2.66–12.37) ng/mL) and were similar to HC levels (1.40 (1.23–1.89) ng/mL).Conclusion. These results suggest an imbalance between pro- and anti-inflammatory innate immune pathways in SFSS. Modulation of the HMGB1-RAGE axis may represent a future therapeutic avenue in this condition.

scholarly journals Xuebijing Ameliorates Sepsis-Induced Lung Injury by Downregulating HMGB1 and RAGE Expressions in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Qiao Wang ◽  
Xin Wu ◽  
Xiaowen Tong ◽  
Zhiling Zhang ◽  
Bing Xu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Molecular Mechanisms ◽  
Weight Ratio ◽  
High Mobility ◽  
Dry Weight ◽  
Neutrophil Infiltration ◽  
Beneficial Effects ◽  
Glycation End Products ◽  
Underlying Mechanisms ◽  
Caecal Ligation And Puncture

Xuebijing (XBJ) injection, a traditional Chinese medicine, has been reported as a promising approach in the treatment of sepsis in China. However, its actual molecular mechanisms in sepsis-induced lung injury are yet unknown. Therefore, this study aimed to investigate the beneficial effects of XBJ on inflammation and the underlying mechanisms in a model of caecal ligation and puncture-(CLP-) induced lung injury. The mice were divided into CLP group, CLP+XBJ group (XBJ, 4 mL/kg per 12 hours), and sham group. The molecular and histological examinations were performed on the lung, serum, and bronchoalveolar lavage (BAL) fluid samples of mice at the points of 6, 24, and 48 hours after CLP. The results show that XBJ reduces morphological destruction and neutrophil infiltration in the alveolar space and lung wet/dry weight ratio, which improves mortality of CLP-induced lung injury. Meanwhile, XBJ treatment downregulates high mobility group box protein 1 (HMGB1) and the receptor for advanced glycation end products (RAGE) expression, as well as neutrophil counts, production of IL-1β, IL-6, and TNF-αin the BAL fluids. In conclusion, these results indicate that XBJ may reduce the mortality through inhibiting proinflammatory cytokines secretion mediated by HMGB1/RAGE axis.

scholarly journals Lung protective effect of Punicalagin on LPS-induced acute lung injury in mice

2022 ◽  
Author(s):  
Yibin Zeng ◽  
Hongying Zhao ◽  
Tong Zhang ◽  
Chao Zhang ◽  
Yanni He ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Lung Tissue ◽  
White Blood Cells ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Protein Levels ◽  
Anti Inflammation

Background: Punicalagin (Pun) is one of the main bioactive compounds in pomegranate peel, it possesses many properties, including antioxidant, anti-inflammation, and immunosuppressive activities. The study was aimed to investigate the protective effect and mechanisms of Pun on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. Methods and Results: Forty-eight BALB/c male mice were used to establish ALI by intratracheal-instilled 2.4 mg/kg LPS, the mice were randomly divided into model and Pun (10, 20, 40 mg/kg) groups. The other twelve mice were intratracheal-instilled same volume of water as control. After 2 h of receiving LPS, mice were administrated drug through intraperitoneal injection. Lung index, histopathological changes, white blood cells and biomarkers in bronchoalveolar lavage fluid (BALF) were analyzed. The protein expression of total and phosphor p65, IκBα, ERK1/2, JNK and p38 in lung tissue was detected. The result showed that Pun could reduce the lung index and wet/dry weight ratio, improve lung histopathological injury. In addition, Pun decreased the inflammation cells and regulated the biomarkers in BALF. Furthermore, Pun dose-dependently reduced the phosphor protein levels of p65, IκBα, ERK1/2, JNK and p38 in lung tissue, which exhibited that the effect of Pun related to MAPKs pathway. More importantly, there is no toxicity was observed in the acute toxicity study of Pun. Conclusion: Pun improves LPS-induced ALI mainly through its anti-inflammatory properties, which is associated with NF-κB and MAPKs signaling pathways. The study implied that Pun maybe a potent agent against ALI in future clinic.

scholarly journals Shen-su-yin, a Traditional Herbal Medicine, Attenuates Lipopolysaccharide-induced Acute Lung Injury in Rats Through Its Anti-inflammatory and Anti-oxidative Effects

2021 ◽  
Author(s):  
Peng Xiao ◽  
Jun Ke ◽  
Jiuyun Zhang ◽  
Haijun Zhou ◽  
Wuhong Zheng
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Oxygenation Index ◽  
Dry Weight ◽  
Signalling Pathway ◽  
Lung Injury Score ◽  
High Dose ◽  
Histopathological Analysis ◽  
Anti Inflammatory

Abstract Most components of Shen-su-yin (SSY), an herbal formula, have anti-inflammatory and antioxidant activities. The present study was designed to investigate potential effects and mechanisms of SSY on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. 48 rats were randomly divided into 4 groups: control (Ctrl) group, LPS-induced ALI group, low- (SSY-LD) and high- (SSY-HD) dose SSY-treated ALI group. SSY was administered to SSY-treated rats immediately after LPS induction. After 24 hours, blood gas analysis and lactate determination were performed; and bronchoalveolar lavage fluid was collected for detecting protein concentration and levels of cytokines. Lung tissues were obtained for Western blot analysis, histopathological analysis, wet-to-dry weight ratio calculation and measurement of oxidative stress levels. SSY improved oxygenation index and mean arterial pressure, decreased levels of lactate and heart rate, alleviated lung histopathology indexes including lung injury score, wet-to-dry weight ratio and exudation of protein as well as inflammatory cells in ALI rats. Furthermore, SSY reduced levels of pro-inflammatory and oxidative mediums, while increasing levels of anti-inflammatory cytokine and anti-oxidative activity in lung tissues. SSY also suppressed NF-κB signalling pathway and further activated Keap1-Nrf2-ARE signalling pathway activated by LPS. Moreover, all the effects caused by SSY in the SSY-HD group were more encouraging than those in the SSY-LD group. The results indicate that the preventive use of SSY can alleviate ALI through the anti-inflammatory and antioxidant effects mediated by inhibition of NF-κB signalling pathway and activation of Keap1-Nrf2-ARE signalling pathway, and the effect of high dose is better.

scholarly journals Mitochondrial Coenzyme Q Protects Sepsis-Induced Acute Lung Injury by Activating PI3K/Akt/GSK-3β/mTOR Pathway in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ruirui Li ◽  
Tao Ren ◽  
Jianqiong Zeng
Keyword(s):  
Acute Lung Injury ◽  
Survival Rate ◽  
Lung Injury ◽  
Lung Tissue ◽  
Coenzyme Q ◽  
Cecal Ligation ◽  
Dry Weight ◽  
Mtor Pathway ◽  
Alveolar Wall ◽  
Pi3k Inhibitor Ly294002

The aim of our study was to assess the effects of mitochondrial coenzyme Q (MitoQ) on sepsis-induced acute lung injury (ALI) and investigate its possible mechanisms. The cecal ligation and puncture (CLP) method was used to establish a septic ALI model. Rats were randomly divided into Con group, CLP group, MitoQ group, and MitoQ + LY294002 group. The survival rate of the rats was recorded, and the survival rate curve was plotted. Moreover, the ratio of wet/dry weight (W/D) in lung tissue was measured. The activity of myeloperoxidase (MPO) was measured by using the MPO colorimetric activity assay kit. The levels of high-mobility group box 1 (HMGB1) and interleukin-6 (IL-6), macrophage inflammatory protein 2 (MIP2), and keratinocyte chemoattractant (KC) were analyzed by ELISA. The histopathological changes were measured by HE staining, and the lung injury was scored. TUNEL assay was applied to detect the apoptotic cells in lung tissue. The protein expressions were detected by western blot. MitoQ increased the survival rate and alleviated pulmonary edema in septic ALI rats. In addition, MitoQ inhibited the MPO activity and decreased the levels of HMGB1 and IL-6. After treatment with MitoQ, alveolar wall edema, inflammatory cell infiltration, and red blood cell exudation were relieved. MitoQ inhibited cell apoptosis in lung tissue of septic ALI rats. Meanwhile, MitoQ treatment remarkedly increased the expression of p-Akt, p-GSK-3β, and p-mTOR but decreased Bax, caspase-3, caspase-9, Beclin-1, and LC-3II/LC-3I. The effects of MitoQ were significantly reversed by the PI3K inhibitor (LY294002). Our study demonstrated that MitoQ could protect sepsis-induced acute lung injury by activating the PI3K/Akt/GSK-3β/mTOR pathway 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.

scholarly journals Thaliporphine Derivative Improves Acute Lung Injury after Traumatic Brain Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Gunng-Shinng Chen ◽  
Kuo-Feng Huang ◽  
Chien-Chu Huang ◽  
Jia-Yi Wang
Keyword(s):  
Traumatic Brain Injury ◽  
Acute Lung Injury ◽  
Brain Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lung Injury Score ◽  
Injury Score ◽  
Aqp4 Expression ◽  
Protein Levels

Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI.

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