Acute lung injury is a kind of common complication after cardiopulmonary bypass. Acute lung injury is attributed to the ischemia-reperfusion injury and systemic inflammatory response syndrome. Several factors common in cardiac surgery with cardiopulmonary bypass may worsen the risk for acute lung injury including atelectasis, transfusion requirement, older age, heart failure, emergency surgery and prolonged duration of bypass. Targets for prevention of acute lung injury include mechanical, surgical and anesthetic interventions that aim to reduce the contact activation, systemic inflammatory response, leukocyte sequestration and hemodilution associated with cardiopulmonary bypass. We aim to review the etiology, risk factors and lung protective strategies for acute lung injury after cardiopulmonary bypass.
Acute lung injury is one of the common and serious complications of acute aortic dissection, and it greatly affects the recovery of patients. Old age, overweight, hypoxemia, smoking history, hypotension, extensive involvement of dissection and pleural effusion are possible risk factors for the acute lung injury before operation. In addition, deep hypothermia circulatory arrest and blood product infusion can further aggravate the acute lung injury during operation. In this paper, researches on risk factors, prediction model, prevention and treatment of acute aortic dissection with acute lung injury were reviewed, in order to provide assistance for clinical diagnosis and treatment.
Objective To investigate the effects of wedelolactone (WEL) on lipopolysaccharide (LPS)-induced pyroptosis of alveolar epithelial cells and AMP-activated protein kinase/nucleotide binding oligomeric domain like receptor 3 (NLRP3)/cysteinyl aspartate specific proteinase-1 (Caspase-1) signaling pathway. Methods Human lung epithelial cells BEAS-2B were treated with 5 - 200 μmol/L wedelolactone, and cell activity was detected using MTT assay. The alveolar epithelial cells were divided into control group, lipopolysaccharide group (LPS group), 10 μmol/L wedelolactone group (WEL-L group), 20 μmol/L wedelolactone group (WEL-M group), 40 μmol/L wedelolactone group (WEL-H group), 40 μmol/L wedelolactone+10 μmol/L AMPK inhibitor Compound C group (WEL-H+Compound C group), and 20 μmol/L Caspase-1 inhibitor Z-YVAD-FMK group (Z-YVAD-FMK group). Transmission electron microscopy was applied to observe the microstructure of cells. ELISA was applied to detect levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-8 (IL-8). Immunofluorescence was applied to detect Caspase-1 and gasdermin family proteins (DGSDMD). Western blot was applied to detect protein expression levels of AMPK, NLRP3, and Caspase-1. Results Wedelolactone concentrations of 10, 20 and 40 μmol/L were selected for follow-up experiments. Compared with Control group, LPS group showed decreased cell activity, severe damage, cell contraction, mitochondrial ridge breakage and decreased number, increased levels of TNF-α, IL-1β, IL-8 and GSDMD, NLRP3, Caspase-1 expression, and decreased p-AMPK/AMPK expression (P<0.05). Wedelolactone treatment could significantly improve LPS-induced pyrosis of alveolar epithelial cells (P<0.05). Compound C could partially reverse the effect of wedelactone on LPS-induced pyrodeath of alveolar epithelial cells (P<0.05). Z-YVAD-FMK treatment also significantly improved LPS-induced pyroptosis of alveolar epithelial cells (P<0.05). Conclusion Wedelolactone can inhibit LPS-induced pyroptosis of pulmonary alveolar epithelial cells by inhibiting AMPK/NLRP3/Caspase-1 signaling pathway.
Lung injury could be classified as acute and chronic injuries, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. Lung function recovery mainly depends on inflammation adjusting, lung and airway remodeling, endogenous stem cell proliferation and differentiation, and tissue repair. The principles of clinical therapy include inhibition of inflammation, balancing coagulation and fibrinolysis, and protective lung ventilation for acute lung injury; while reduction of hyper-secretion, bronchodilation, adjusting airway mucosal inflammation and immunity, as well as improving airway remodeling for chronic obstructive pulmonary disease. The functional recovery of lung and airway depends on endogenous stem cell proliferation and repair. The purpose of clinical treatment is to provide assistance for lung and airway repair besides pathophysiological improvement.
Seawater drowning leads to acute lung tissue structure injury, lung ventilation and air exchange dysfunction, acute pulmonary edema, and even acute respiratory failure. The pathogenesis of seawater induced acute lung injury is complex, involving inflammatory response, pulmonary edema, pulmonary surfactant, oxidative stress, apoptosis and autophagy. Timely and effective treatment is the key to reduce the mortality and disability rate of patients with seawater induced acute lung injury. This article summarizes the research progress in the pathogenic mechanism and treatment strategy of seawater induced acute lung injury, aiming to provide reference for the comprehensive treatment of seawater induced acute lung injury patients in clinical work and subsequent related research.
Objective To investigate the effect of non-coding RNA activated by DNA damage (NORAD) on acute lung injury (ALI) in septic rats by regulating the miR-155-5p/TLR6 molecular axis. Methods The rats were randomly divided into control group, model group, low NORAD expression no-load group (LV-sh-NC), low NORAD expression group (LV-sh-NORAD), low NORAD expression +miR-155-5p low expression no-load group (LV-sh-NORAD+NC antagomir), NORAD low expression +miR-155-5p low expression group (LV-sh-NORAD+miR-155-5p antagomir). ELISA kits were applied to detect interleukin (IL)-8, IL-1β, and tumor necrosis factor-α (TNF-α) levels; quantitative real-time polymerase chain reaction was applied to detect the expression of NORAD, miR-155-5p, and Toll-like receptor 6 (TLR6) genes in lung tissue of rats in each group. The ratio of wet weight to dry weight (W/D) of lung tissue was measured. The pathological changes of lung tissue were observed by hematoxylin-eosin staining, and apoptosis in lung tissue cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. Western blot was applied to detect the expressions of TLR6, Bax, Bcl-2, and cleaved cysteinyl aspartate specific proteinase 3 caspase-3) proteins in cells. Dual luciferase reporter gene experiment was applied to verify the relationship between miR-155-5p and NORAD and TLR6. Results Compared with the control group, the lung tissue of rats in the model group and LV-sh-NC group was obviously damaged, the levels of serum IL-1β, TNF-α, IL-8, expression of NORAD and TLR6 mRNA in lung tissue, W/D ratio, apoptosis rate, expression of TLR6, Bax, and Cleaved-caspase-3 proteins were obviously increased, the expression of miR-155-5p and Bcl-2 proteins in lung tissue was obviously reduced (P<0.05). Down-regulation of NORAD expression could reduce lung tissue injury, serum IL-1β, TNF-α, IL-8 levels, mRNA expression of NORAD and TLR6 in lung tissue, W/D ratio, apoptosis rate, TLR6, Bax, Cleaved caspase-3 protein expression, and cleaved caspase-3 protein expression. The expression of miR-155-5p and Bcl-2 protein in lung tissue were significantly increased (P<0.05). Down-regulating the expression of miR-155-5p could reduce the improvement effect of negatively regulated NORAD on sepsis ALI rats (P<0.05). Conclusion Interference with NORAD can alleviate lung injury in ALI rats by regulating the miR-155-5p/TLR6 molecular axis.
ObjectiveTo investigate the value of chest high-resolution computed tomography (HRCT) score in evaluating the severity of hip fracture-induced early acute lung injury (ALI) in the elderly patients.MethodsThe clinical data of 289 elderly hip fracture patients in Chongqing Traditional Chinese Medicine Hospital from July 2014 to April 2020 were retrospectively analyzed. All patients were divided into two groups, including an ALI group (n=114, 36 males and 78 females at age of 82.94±6.85 years) and a non-ALI group (n=175, 51 males and 124 females at age of 84.42±6.31 years). General information, chest HRCT scores and PaO2/FiO2 were compared between the two groups. Correlation analysis was used to compare the relationship between chest HRCT scores and PaO2/FiO2. Multiple linear stepwise regression analysis was applied to evaluate the effective extent of the diffuse ground glass opacity (DGGO), intense parenchymal opacification (IPO), and reticulation HRCT scores to the overall HRCT scores.ResultsThe DGGO scores, IPO scores, reticulation scores, overall HRCT scores and PaO2/FiO2 were higher in the ALI group than those in the non-ALI group (P<0.001). In the ALI group, correlation analysis showed that DGGO, overall HRCT scores were in significantly negative correlation with PaO2/FiO2 (P<0.001). In addition, the correlation among PaO2/FiO2 and overall HRCT scores was more significant than that of DGGO scores. Multiple stepwise regression analysis indicated that DGGO, IPO, and reticulation scores were independent influencing factors for overall HRCT scores. Among the influencing factors, DGGO scores had the greatest impact, then IPO scores and reticulation scores. The HRCT signs of DGGO, IPO, and reticulation appeared simultaneously had the greatest effects on the overall HRCT scores.ConclusionThe chest HRCT score, which is associated with PaO2/FiO2, also can be used in the severity assessment of elderly patients with early ALI caused by hip fracture.
Sepsis-associated organ dysfunction arises from uncontrolled inflammation and immune dysregulation, causing microcirculatory impairment and multi-organ failure. Stellate ganglion block (SGB) may confer organ protection by regulating the sympathetic nervous system and hypothalamic-pituitary-adrenal axis to suppress excessive inflammation and oxidative stress. Available evidence, mainly from experimental and small clinical studies, suggests potential benefits of SGB in sepsis-induced acute lung injury, ventricular arrhythmias, and limb ischemia, which require confirmation in multicenter randomized controlled trials. This review outlines the mechanisms and clinical advances of SGB in sepsis-related organ dysfunction, providing a theoretical basis for its application in critical care.
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是指由心源性以外的各种肺内外致病因素所导致的急性进行性缺氧性呼吸衰竭，它们具有性质相同的病理生理改变，严重的ALI或ALI的最终严重阶段被定义为ARDS，临床表现以呼吸窘迫、顽固性低氧血症和非心源性肺水肿为特征，采用常规的治疗难以纠正其低氧血症，死亡率高达60%。目前，有关ALI/ARDS的研究取得较多进展，其中，能有效评估ALI病情和预测死亡率的临床参数和生化指标一直是研究热点。
Objective To investigate the effect and potential mechanism of bone marrow mesenchymal stem cells (BMSCs) - derived extracellular vesicles (EVs) on lung tissue injury in mice with severe acute pancreatitis (SAP). Methods A total of 24 specific pathogen free grade male C57BL/6 mice and primary mouse lung microvascular endothelial cells (PMVECs) were selected. The mice were divided into sham group, SAP group, and BMSC group, with 8 mice in each group. The mouse primary PMVECs were divided into model group [sodium taurocholate (NaTC) group], BMSC-EV group, and control group. Extraction and characterization of healthy mouse BMSCs and their derived extracellular vesicles (BMSC-EVs) were conducted. A mouse model of SAP was established, and BMSC-EVs were injected into SAP mice by tail vein or intervened in PMVECs in vitro, to observe the pathological damage of pancreatic and lung tissues, the changes of serum amylase, lipase, and inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-6 (IL-6)], the expression of inflammatory factors of lung tissues and PMVECs, and the endothelial cell barrier related proteins [E-cadherin, ZO-1, intercellular cell adhesion molecule-1 (ICAM-1)], and tight junctions between PMVECs to explore the effects of BMSC-EVs on pancreatic and lung tissues in SAP mice and PMVECs in vitro. Results BMSCs had the potential for osteogenic, chondrogenic, and lipogenic differentiation, and the EVs derived from them had a typical cup-shaped structure with a diameter of 60-100 nm. BMSC-EVs expressed the extracellular vesicle-positive proteins TSG101 and CD63 and did not express the negative protein Calnexin. Compared with the mice in the sham group, the SAP mice underwent significant pathological damage to the pancreas (P<0.05), and their serum amylase, lipase, inflammatory factor IL-6, and TNF-α levels were significantly up-regulated (P<0.05); whereas, BMSC-EVs markedly ameliorated the pancreatic tissue damage in the SAP mice (P<0.05), down-regulated the levels of peripheral serum amylase, lipase, IL-6 and TNF-α (P<0.05), and up-regulated the level of anti-inflammatory factor IL-10 (P<0.05). In addition to this, the SAP mice showed significant lung histopathological damage (P<0.05), higher neutrophils and macrophages infiltration (P<0.05), higher levels of the inflammatory factors TGF-β and IL-6 (P<0.05), as well as reduced barrier protein E-cadherin, ZO-1 expression and elevated expression of ICAM-1 (P<0.05). BMSC-EVs significantly ameliorated lung histopathological injury, inflammatory cells infiltration, inflammatory factor levels, and expression of barrier proteins, and suppressed ICAM-1 expression (P<0.05). In the in vitro PMVECs experiments, it was found that intercellular tight junctions were broken in the NaTC group, and the levels of inflammatory factors TNF-α and IL-6 were significantly up-regulated (P<0.05), the protein expression of E-cadherin and ZO-1 was significantly down-regulated (P<0.05), and the expression of ICAM-1 was significantly up-regulated (P<0.05). BMSC-EVs significantly improved intercellular tight junctions in the NaTC group and inhibited the secretion of TNF-α and IL-6 (P<0.05), up-regulated the expression of the barrier proteins E-cadherin and ZO-1, and down-regulated the expression of ICAM-1 (P<0.05). Conclusion BMSC-derived EVs ameliorate lung tissue injury in SAP mice by restoring the lung endothelial cell barrier and inhibiting inflammatory cell infiltration.