Edema pulmonar por reexpansión. Reporte de Caso / Pulmonary edema due to re-expansion. Case Report

Introducción. El edema pulmonar por reexpansión es una complicación poco frecuente, secundaria a una rápida reexpansión pulmonar posterior al drenaje por toracentesis o toracostomía cerrada. Al día de hoy, se ha descrito una incidencia menor al 1 % tras toracostomía cerrada, con mayor prevalencia en la segunda y tercera década de la vida. Su mecanismo fisiopatológico exacto es desconocido; se ha planteado un proceso multifactorial de daño intersticial pulmonar asociado con un desequilibrio de las fuerzas hidrostáticas. Caso clínico. Presentamos el caso de un paciente que desarrolló edema pulmonar por reexpansión posterior a toracostomía cerrada. Se hizo una revisión de la literatura sobre esta complicación. Resultados. Aunque la clínica sugiere el diagnóstico, la secuencia de imágenes desempeña un papel fundamental. En la mayoría de los casos suele ser autolimitado, por lo que su manejo es principalmente de soporte; sin embargo, se han reportado tasas de mortalidad que alcanzan hasta el 20 %, por tanto, es importante conocer los factores de riesgo y las medidas preventivas. Conclusión. El edema pulmonar de reexpansión posterior a toracostomía es una complicación rara en los casos con neumotórax, aunque es una complicación que se puede presentar en la práctica diaria, por lo cual debe tenerse en mente para poder hacer el diagnóstico y un manejo adecuado.

Introduction. Re-expansion pulmonary edema is a rare complication secondary to rapid pulmonary re-expansion after drainage by thoracentesis and/or closed thoracostomy. As of today, an incidence of less than 1% has been described after closed thoracostomy, with a higher prevalence in the second and third decades of life. Its exact pathophysiological mechanism is unknown; a multifactorial process of lung interstitial damage associated with an imbalance of hydrostatic forces has been proposed. Clinical case. We present the case of a patient who developed pulmonary edema due to re-expansion after closed thoracostomy, conducting a review of the literature on this complication. Results. Although the clinic suggests the diagnosis, the sequence of images plays a fundamental role. In most cases, it tends to be a self-limited disease, so its management is mainly supportive. However, mortality rates of up to 20% have been recorded. Therefore, it is important to identify patients with major risk factors and initiate preventive measures in these patients. Conclusions. Re-expansion pulmonary edema after thoracostomy is a rare complication in cases with pneumothorax; however, it is a complication that can occur in daily practice. Therefore, it must be kept in mind to be able to make the diagnosis and an adequate management.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism.@*METHODS@#Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis.@*RESULTS@#DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01).@*CONCLUSIONS@#DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Protective Effect of Zingiberis Rhizoma Recens on LPS-induced Acute Lung Injury in Mice Through TLR4/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the protective effect and mechanism of Zingiberis Rhizoma Recens alcohol extract on lipopolysaccharide （LPS）-induced acute lung injury in mice. MethodBalb/c mice were randomly divided into normal group， model group， dexamethasone group， and low- and high-dose Zingiberis Rhizoma Recens groups. Mice in the normal group were instilled with normal saline through the nose， and the other groups were instilled with normal saline containing LPS （50 μg）. After 30 minutes of modeling， the dexamethasone group was gavaged with 5 mg·kg-1 of dexamethasone acetate solution， the low- and high-dose Zingiberis Rhizoma Recens groups were gavaged with different doses of （7， 14 g·kg-1） of Zingiberis Rhizoma Recens alcohol extract， and the normal group and the model group were gavaged with the same volume of water. After 24 hours of modeling， the total number of white blood cells in bronchoalceolar lavage fluid （BALF） was detected by cell counter， and the levels of the inflammatory factors including tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and superoxide dismutase （SOD）， and myeloperoxidase （MPO） was detected by enzyme-linked immunosorbent assay （ELISA）. Haematoxylin-eosin （HE） staining method was used to observe the pathological changes of lung tissue in each group， and the Western blot was used to detect the protein expression of nuclear transcription factor （NF）-κB p65， phosphorylation （p）-NF-κB p65， and Toll-like receptor 4 （TLR4） in lung tissue. ResultCompared with the normal group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the model group was increased （P<0.01）， and the level of SOD was decreased （P<0.05）. Pathological damage of lung tissue was obvious， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was increased （P<0.01）. Compared with the model group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the treatment group was decreased （P<0.05，P<0.01）， and the level of SOD was increased （P<0.05，P<0.01）. Pathological damage of lung tissue was alleviated， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was decreased （P<0.01）. ConclusionZingiberis Rhizoma Recens alcohol extract may play a protective role in LPS-induced acute lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.

Xuebijing improves inflammation and pyroptosis of acute lung injury by up-regulating miR-181d-5p-mediated SPP1 inactivation

Abstract Background Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI. Methods The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 μg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay. Results XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis. Conclusion XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Lesión pulmonar aguda producida por transfusión (TRALI): Reporte de caso

Introducción: La lesión pulmonar aguda (TRALI) y la sobrecarga circulatoria (TACO) son las principales causas de morbilidad y mortalidad relacionadas con la transfusión. La TRALI se presenta durante o después de las transfusiones de plasma y sus derivados, o por inmunoglobulinas en alta concentración intravenosa; se asocia a procesos sépticos, cirugías y transfusiones masivas. La TACO es la exacerbación de manifestaciones respiratorias en las primeras 6 horas postransfusión. Reporte caso: Paciente de sexo masculino de 38 días de vida, ingresó al servicio de urgencias con un cuadro clínico de 8 días de evolución, caracterizado por dificultad respiratoria dado por retracciones subcostales y aleteo nasal sin otro síntoma asociado, con antecedentes de importancia de prematuridad y bajo peso al nacer. El reporte de hemograma arrojó cifras compatibles con anemia severa, por lo que requirió transfusión de glóbulos rojos empaquetados desleucocitados. El paciente presentó un cuadro respiratorio alterado en un periodo menor a 6 horas, por lo que se descartaron causas infecciosas y finalmente se consideró cuadro compatible con TRALI. Conclusiones: Se debe considerar una lesión pulmonar aguda relacionada con una transfusión de sangre si se produce una insuficiencia respiratoria aguda durante o inmediatamente después de la infusión de hemoderivados que contienen plasma.

Introduction: Acute lung injury (TRALI) and circulatory overload (TACO) are the main causes of transfusion-related morbidity and mortality. TRALI occurs during or after transfusions of plasma or its derivatives, or by immunoglobulins in high intravenous concentration; it is associated with septic processes, surgeries, and massive transfusions. TACO is the exacerbation of respiratory manifestations in the first 6 hours post transfusion. Case report: A 38-day-old male was admitted to the emergency department with clinical symptoms experienced over the course of 8 days and characterized by respiratory distress due to subcostal retractions and nasal flaring with no other associated symptoms. Important antecedents included prematurity and low birth weight. The hemogram report showed figures compatible with anemia, which benefited from transfusion of packed red blood cells without leukocytes. In a period of less than 6 hours, the patient presented altered respiratory symptoms, practitioners ruled out infectious causes and finally considered clinical signs compatible with TRALI. Conclusion: Acute lung injury related to blood transfusion should be considered if acute respiratory failure occurs during or immediately after infusion of plasma-containing blood products.

Ischemic Postconditioning Attenuates Myocardial Ischemia-Reperfusion-Induced Acute Lung Injury by Regulating Endoplasmic Reticulum Stress-Mediated Apoptosis

ABSTRACT Objective: To explore the effect of ischemic postconditioning on myocardial ischemia-reperfusion-induced acute lung injury (ALI). Methods: Forty adult male C57BL/6 mice were randomly divided into sham operation group (SO group), myocardial ischemia-reperfusion group (IR group), ischemic preconditioning group (IPRE group) and ischemic postconditioning group (IPOST group) (10 mice in each group). Anterior descending coronary artery was blocked for 60 min and then reperfused for 15 min to induce myocardial IR. For the IPRE group, 3 consecutive cycles of 5 min of occlusion and 5 minutes of reperfusion of the coronary arteries were performed before ischemia. For the IPOST group, 3 consecutive cycles of 5 min reperfusion and 5 minutes of occlusion of the coronary arteries were performed before reperfusion. Pathological changes of lung tissue, lung wet-to-dry (W/D) weight ratio, inflammatory factors, oxidative stress indicators, apoptosis of lung cells and endoplasmic reticulum stress (ERS) protein were used to evaluate lung injury. Results: After myocardial IR, lung injury worsened significantly, manifested by alveolar congestion, hemorrhage, structural destruction of alveolar septal thickening, and interstitial neutrophil infiltration. In addition, lung W/D ratio was increased, plasma inflammatory factors, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17A, were increased, malondialdehyde (MDA) activity of lung tissue was increased, and superoxide dismutase (SOD) activity was decreased after myocardial IR. It was accompanied by the increased protein expression levels of ERS-related protein glucose regulatory protein 78 (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), and caspase-12, and the increased apoptotic indices of lung tissues. Conclusion: IPOST can effectively improve myocardial IR-induced ALI by inhibiting ERS-induced apoptosis of alveolar epithelial cells.

Protective effect of luteolin on acute lung injury induced by extracorporeal circulation and its mechanism / 中国胸心血管外科临床杂志

@#Objective    To investigate the protective effect of atomized inhalation of nano-luteolin preparation on acute lung injury caused by extracorporeal circulation, and to explore the anti-inflammatory mechanism of luteolin, so as to provide study basis for clinical application. Methods    Thirty male SD rats aged 5-6 weeks and weighting 160-190 g, were randomly divided into a preoperative baseline (BL) group, arteriovenous partial diversion (ECC) group, luteolin atomization pretreatment for 1 h group, 2 h group, and 3 h group by random number method, with 6 rats in each group. In the BL group, lung tissue samples were collected directly without any treatment. The ECC group received mechanical ventilation, and the whole body was heparinized after the jugular arteriovenous intubation. The flow was transferred for 30 minutes, followed by observation for 60 minutes, then lung tissue samples were collected. Subjects in the 1 h, 2 h and 3 h groups were placed in a small animal atomizer 1 h, 2 h and 3 h before flow transfer respectively, and the subsequent operation was the same as that in the ECC group. The inflammatory level of lung tissue was detected to evaluate the degree of pathological injury of lung tissue. Western blotting (WB) was used to detect the contents of p65, IKKα, IKKβ and IKKγ in the cytoplasm of lung tissue samples of each group. Results    Compared with the ECC group, the levels of IL-6 and TNF-α in lung tissues and the degree of pathological injury in the 1 h, 2 h and 3 h groups decreased, and the difference between the 3 h group and the ECC group was statistically different (P<0.05). WB results showed that compared with the ECC group, the levels of p65 in lung tissue of the 1 h, 2 h and 3 h groups decreased; the levels of IKKβ in the lung tissue increased in the 1 h, 2 h and 3 h groups, and the difference of the 3 h group was statistically different from the ECC group (P<0.05). Conclusion    Luteolin has a protective effect on acute lung injury induced by ECC, and atomization 3 h in advance has the best protective effect on lung. The mechanism plays a protective role in ECC-induced acute lung injury, may be through inhibition of IKKβ phosphorylation, thereby inhibiting the classical NF-κB signaling pathway.

Clearance effect of regulation of serine/threonine protein kinase-1 signaling pathway by insulin on pulmonary edema in mice with acute lung injury / 中国生物制品学杂志

@#Objective To investigate the mechanism of insulin alleviating pulmonary edema in mice with acute lung injury(ALI) by serine/threonine protein kinase-1(SGK1).Methods 32 male adult C3H/HeN mice were randomly divided into control group(only pumped with the same amount of normal saline as the treatment group),ALI group(continuously pumped with the same amount of normal saline as the treatment group after modeling),treatment group [continuously pumped with 0.1 U/(kg·h) of insulin through jugular vein after establishing ALI model] and SGK1 siRNA group[continuously pumped with 0.1 U/(kg·h) of insulin and given SGK1 siRNA(75 μg SGK1 siRNA diluted in 100 μL saline) simultaneously after establishing ALI model] with 8 mice in each group.After 8 h,the mice were killed for arterial blood gas analysis(1 h after establishment of the model) and the changes of plasma glucose levels were detected(0,1,4and 8 h);The bronchoalveolar lavage fluid(BALF) was collected to detect the content of total protein,and the alveolar epithelial permeability and lung water content were measured;The pathological changes of lung tissue and apoptosis of lung epithelial cells were observed;The protein expressions of alveolar epithelial sodium channel(ENaC) and α_1-Na~+,K~+-ATPase and the phosphorylation level of SGK1 were determined by Western blot.Results There was no significant difference in plasma glucose level of ALI and treatment group at 0,1,4 and 8 h after insulin infusion(t=1.330 0,0.986 0,0.565 7 and 0.724 3,P=0.204 7,0.340 7,0.580 6 and 0.480 8,respectively).Compared with ALI group,the partial pressure of oxygen in arterial blood in treatment group increased significantly(t=6.026,P <0.000 1),while the BALF protein content,alveolar epithelial permeability,lung water content and lung epithelial cells apoptosis decreased significantly(t=7.39,5.286,5.651 and 3.312,P <0.000 1,=0.000 4,=0.000 2 and=0.007 8,respectively),and the expression of α-ENaC and α_1-Na~+,K~+-ATPase and the phosphorylation level of SGK1 in lung tissue significantly increased(t=26,18.67 and 8.547,P <0.000 1,<0.000 1 and=0.000 1,respectively);Compared with the treatment group,the BALF protein content,alveolar epithelial permeability,lung water content and lung epithelial cells apoptosis increased significantly in SGK1 siRNA group(t=5.964,3.449,3.148 and 3.520,P=0.000 2,0.006 2,0.010 4 and0.016 9,respectively),while α-ENaC and α_1-Na~+,K~+-ATPase protein expression and SGK1 phosphorylation level decreased significantly(t=13,9.874 and 7.741,P <0.000 1,<0.000 1 and=0.001 5,respectively).Conclusion Exogenous insulin can alleviate the pulmonary edema in ALI mice,which might be mediated via up-regulation of the expressions of α-ENaC and α_1-Na~+,K~+-ATPase by SGK1.

Role of PIAS-regulated SUMOylation of PPARγ in endogenous protective mechanism against endotoxin-induced acute lung injury in mice / 中华麻醉学杂志

Objective:To evaluate the role of small ubiquitin-associated modifier (SUMO) E3 ligase (PIAS)-regulated SUMOylation of peroxisome proliferator-activated receptor γ (PPARγ) in the endogenous protective mechanism against endotoxin-induced acute lung injury (ALI) in mice.Methods:Experiment Ⅰ Twenty-four clean-grade wild type male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (C group), ALI group, ALI+ PPARγ inducer TZD group (ALI+ T group) and ALI+ TZD+ SUMOylation inhibitor anacardic acid group (ALI+ T+ A group). Lipopolysaccharide (LPS) 15 mg/kg was injected into the tail vein to develop the ALI model. In ALI+ T+ A group, anacardic acid 5 mg/kg was intraperitoneally injected at 1 h before LPS administration. In ALI+ T group and ALI+ T+ A group, TZD 50 mg/kg was intraperitoneally injected at 30 min before LPS administration. The mice were sacrificed at 12 h after LPS administration, and the lung tissues were obtained to examine the pathological changes which were scored and to determine the wet/dry (W/D) weight ratio, and expression of PIAS1, PIAS2, PIAS3 and PIASy protein and mRNA (by Western blot or polymerase chain reaction). Experiment Ⅱ Mouse alveolar macrophages (MH-S cells) were cultured in vitro and divided into 4 groups ( n=5 each) using a random number table method: control group (C group), LPS group, LPS+ PIAS2 siRNA group (L+ P group) and LPS+ Con siRNA group (L+ C group). Cells were routinely cultured in group C. Cells were stimulated with 10 μg/ml LPS to develop the model of endotoxin challenge. PIAS2 siRNA 50 nmol/L and Con siRNA 50 nmol/L were transfected at 48 h before LPS was added in L+ P group and L+ C group, respectively. The cells were collected at 24 h of incubation with LPS to determine the cell viability, levels of M1 and M2 alveolar macrophages (by flow cytometry), expression of PIAS2 and PPARγ (by Western blot), co-expression of PPARγ-SUMO1 (by immunoprecipitation) and expression of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) mRNA (by polymerase chain reaction). The ratio of M1/M2 was calculated. Results:Experiment Ⅰ Compared with C group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was up-regulated in the other three groups ( P<0.05). Compared with ALI group, the lung injury scores and W/D ratio were significantly decreased, and the expression of PIAS2 protein and mRNA was up-regulated in ALI+ T group and ALI+ T+ A group ( P<0.05). Compared with ALI+ T group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was down-regulated in ALI+ T+ A group ( P<0.05). There was no significant difference in the expression of PIAS1, PIAS3 and PIASy protein and mRNA in lung tissues among the four groups ( P>0.05). Experiment Ⅱ Compared with C group, the cell viability was significantly decreased, the expression of PPARγ and co-expression of PPARγ-SUMO1 was up-regulated, the levels of M1 and M2 macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was up-regulated, and the expression of IL-10 mRNA was down-regulated in the other three groups, and PIAS2 expression was significantly up-regulated in L group and L+ C group ( P<0.05). Compared with L group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and PPARγ-SUMO1 co-expression were down-regulated, the M1 macrophage level and M1/M2 ratio were increased, TNF-α mRNA expression was up-regulated, and the expression of IL-10 mRNA was down-regulated in L+ P group ( P<0.05), and no significant change was found in the parameters mentioned above in L+ C group ( P>0.05). Compared with L+ C group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and co-expression of PPARγ-SUMO1 were down-regulated, the level of M1 alveolar macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was down-regulated, and the expression of IL-10 mRNA was up-regulated in L+ P group ( P<0.05). Conclusions:PIAS2-regulated SUMOylation of PPARγ is the endogenous protective mechanism against endotoxin-induced ALI in mice, which may be related to inhibition of macrophage polarization into M1 type and alleviation of inflammatory responses.

Role of aryl hydrocarbon receptor in down-regulation of Clara cell secretory protein expression during endotoxin-induced lung injury in rats / 中华麻醉学杂志

Objective:To evaluate the role of aryl hydrocarbon receptor (AhR) in the down-regulation of Clara cell secretory protein (CCSP) expression during endotoxin-induced lung injury in rats.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) using a random number table method: normal control group (group C), acute lung injury (ALI) group, ALI+ AhR antagonist group, and ALI+ vehicle group. Lipopolysaccharide(LPS) 1 mg/kg was intratracheally instilled to develop the model of lung injury, while the equal volume of normal saline was given instead in group C. At 2 h before LPS injection, AhR antagonist 6, 2′, 4′-trimethoxyflavone solution 5 mg/kg (diluted to 1 ml in dimethyl sulfoxide solution) was intraperitoneally injected in ALI+ AhR antagonist group, while dimethyl sulfoxide solution 1 ml was given in ALI+ vehicle group. The rats were sacrificed under anesthesia at 48 h after LPS administration. The left lung was lavaged and the broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of CCSP by enzyme-linked immunosorbent assay, and the expression of CCSP in the bronchial epithelium in right lung tissues was determined by immunohistochemistry. Results:Compared with group C, the expression of CCSP in the bronchial epithelium was significantly down-regulated, and the concentrations of CCSP in BALF were decreased in the other three groups ( P<0.05 or 0.01). Compared with ALI group and ALI+ vehicle group, the histopathological injury was significantly reduced, the expression of CCSP in the bronchial epithelium was up-regulated, and the concentrations of CCSP in BALF were increased in ALI+ AhR antagonist group ( P<0.01). Conclusions:AhR partially mediates the down-regulation of CCSP expression during endotoxin-induced lung injury in rats.

Role of α7nAChR in penehyclidine hydrochloride-induced reduction of endotoxin-induced acute lung injury in mice / 中华麻醉学杂志

Objective:To evaluate the role of α7 nicotinic acetylcholine receptor (α7nAChR) in penehyclidine hydrochloride-induced reduction of endotoxin-induced acute lung injury (ALI) in mice.Methods:Forty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-25 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), ALI group, penehyclidine hydrochloride group (PHC group), and α7nAChR inhibitor MLA group (MLA group). ALI was induced by intraperitoneal injection of lipopolysaccharide 15 mg/kg in anesthetized animals, while normal saline was given instead in group C. In PHC group, penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected at 30 min before developing the model. MLA 10 mg/kg was intraperitoneally injected at 10 min before administration of penehyclidine hydrochloride in MLA group. Mice were sacrificed at 6 h after lipopolysaccharide administration, and lung tissues were collected for microscopic examination of the pathological changes (by HE staining) and for determination of the wet/dry weight ratio (W/D ratio), content of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-10 (by enzyme-linked immunosorbent assay) and expression of α7nAChR (by Western blot). Results:Compared with C group, the W/D ratio and contents of TNF-α and IL-1β were significantly increased, the content of IL-10 was decreased, and the expression of α7nAChR was up-regulated in ALI, PHC and MLA groups ( P<0.05). Compared with ALI group, the W/D ratio and contents of TNF-α and IL-1β were significantly decreased, the content of IL-10 was increased, and the expression of α7nAChR was up-regulated in PHC group ( P<0.05). Compared with PHC group, the W/D ratio and contents of TNF-α and IL-1β were significantly increased, the content of IL-10 was decreased, and the expression of α7nAChR was down-regulated in MLA group ( P<0.05). Compared with ALI group, the pathological changes of lung tissues were significantly mitigated in PHC group, while this effect of PHC was partially reversed by α7nAChR inhibitor MLA. Conclusions:α7nAChR is involved in penehyclidine hydrochloride-induced reduction of endotoxin-induced ALI in mice.

Relationship between SIRT1 and ferroptosis during curcumin-induced reduction of acute lung injury in a mouse model of sepsis / 中华麻醉学杂志

Objective:To evaluate the relationship between silent information regulator 1 (SIRT1) and ferroptosis during curcumin-induced reduction of acute lung injury in a mouse model of sepsis.Methods:One hundred and fifty-two SPF-grade male C57BL/6J mice, aged 8 weeks, weighing 23-27 g, were divided into 4 groups ( n=38 each) using a random number table method: sham operation group (C group), sepsis group (S group), curcumin group (Cur group) and curcumin plus SIRT1 inhibitor EX527 group (CE group). Curcumin 200 mg/kg was administered by intragastric gavage every day in Cur group. Curcumin 200 mg/kg was administered by intragastric gavage every day and EX527 5 mg/kg was intraperitoneally injected in CE group. The equal volume of solvent dimethyl sulfoxide (DMSO) was given in C group and S group. Sepsis model was developed by cecal ligation and puncture (CLP) after 5 days of consecutive administration in anesthetized animals. Twenty mice in each group were randomly selected to observe the survival condition within 7 days after CLP. The bronchoalveolar lavage fluid (BALF) was collected at 24 h after developing the model to determine the concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6 and IL-18 (by enzyme-linked immunosorbent assay), and the lung tissues were obtained for microscopic examination of the pathological changes which were scored and for determination of wet-to-dry lung weight (W/D) ratio, contents of glutathione (GSH), malondialdehyde (MDA) and iron (by colorimetry), and expression of SIRT1, glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long chain family member 4 (ACSL4) (by Western blot). Results:Compared with C group, the 7-day survival rate after CLP was significantly decreased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were increased, the content of GSH in lung tissues was decreased, the contents of MDA and iron were increased, the expression of SIRT1 and GPX4 was down-regulated, and the expression of ACSL4 was up-regulated in S group ( P<0.05). Compared with S group, the 7-day survival rate after CLP was significantly increased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were decreased, the content of GSH was increased, the contents of MDA and iron were decreased, the expression of SIRT1 and GPX4 was up-regulated, and the expression of ACSL4 was down-regulated in Cur group ( P<0.05). Compared with Cur group, the 7-day survival rate after CLP was significantly decreased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were increased, the content of GSH was decreased, the contents of MDA and iron were increased, the expression of SIRT1 and GPX4 was down-regulated, and the expression of ACSL4 was up-regulated in CE group ( P<0.05). Conclusions:The mechanism by which curcumin attenuates acute lung injury may be related to activation of SIRT1 and further inhibition of ferroptosis in mice.

Role of ferroptosis in lung injury in a rat model of autologous orthotopic liver transplantation / 中华麻醉学杂志

Objective:To evaluate the role of ferroptosis in lung injury in a rat model of autologous orthotopic liver transplantation.Methods:Twenty-four healthy adult SPF-grade male rats, aged 8-10 weeks, weighing 230-270 g, were divided into 3 groups ( n=8 each) using the random number table method: sham operation group (S group), autologous in situ liver transplantation group (LT group) and ferroptosis inhibitor Ferrostain-1 group (LT+ Fer-1 group). In LT group and LT+ Fer-1 group, an autologous in situ liver transplantation model was developed in anesthetized animals, and Ferrostain-1 5 mg/kg was intraperitoneally injected at 30 min before surgery in LT+ Fer-1 group. The inferior vena cava blood samples were obtained at 6 h of reperfusion, then animals were sacrificed, and lung tissues were obtained. The morphology of lung tissues was examined, and the lung injury was scored. The serum malondialdehyde (MDA) concentration and contents of MDA, reduced glutathione (GSH), glutathione peroxidase4 (GPX4), and Fe 2+ in lung tissues were measured by enzyme-linked immunosorbent assay. The expression of ferritin heavy chain 1 (FTH1) and solute carrier family 7 member 11 recombinant protein (SLC7A11) was determined by Western blot. Results:Compared with S group, the lung injury, serum MDA concentration, and contents of MDA and Fe 2+ were significantly increased, the contents of GSH and GPX4 were decreased, and the expression of FTH1 and SLC7A11 was down-regulated in LT group ( P<0.05). Compared with LT group, the lung injury, serum MDA concentration, and contents of MDA and Fe 2+ were significantly decreased, the contents of GSH and GPX4 were increased, and the expression of FTH1 and SLC7A11 was up-regulated in LT+ Fer-1 group ( P< 0.05). Conclusions:Ferroptosis is involved in the pathophysiology of lung injury in a rat model of autologous orthotopic liver transplantation.

Risk factors for early acute lung injury after pediatric living-related liver transplantation and the predictive value / 中华麻醉学杂志

Objective:To identify the risk factors for early acute lung injury (ALI) after living-related liver transplantation in pediatric patients and evaluate the value of the risk factors in prediction of ALI.Methods:Perioperative data of patients were obtained through the electronic medical records system. Patients were divided into non-ALI group and ALI group according to whether ALI occurred within the first week after surgery. The risk factors of which P values were less than 0.05 would enter the multiple logistic regression analysis to stratify ALI-related risk factors. Area under the ROC curve was used to analyze the value of the risk factors in prediction of postoperative ALI. Results:A total of 67 patients were enrolled, including 45 cases in non-ALI group and 22 cases in ALI group. Increased intraoperative blood transfusion volume and up-regulated expression of miR-122 and miR-21 were independent risk factors for the occurrence of postoperative ALI ( P<0.05), and the area under the ROC curve (95% confidence interval) of serum miR-122 and miR-21 expression was 0.946 (0.875 to 1.00), with sensitivity and specificity of 95% and 90%, respectively. Conclusions:Increased intraoperative blood transfusion volume and up-regulated expression of serum miR-122 and miR-21 are independent risk factors for early postoperative ALI, and serum miR-122 and miR-21 levels have a high value in prediction of the development of postoperative ALI in pediatric patients undergoing living-related liver transplantation.

Effect of intravenous infusion of lidocaine on pulmonary gas exchange function during acute lung injury in septic rats / 中华麻醉学杂志

Objective:To evaluate the effect of intravenous infusion of lidocaine on pulmonary gas exchange function during acute lung injury in septic rats.Methods:Thirty clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 220-280 g, were divided into 3 groups ( n=10 each) using a random number table method: control group (C group), sepsis group (S group) and lidocaine group (L group). Model of acute lung injury in septic rats was prepared by intraperitoneal injection of LPS 10 mg/kg in S and L groups, the equal volume of normal saline was injected in group C, lidocaine was injected at a loading dose of 10 mg/kg via the tail vein at 1 min after LPS injection and then continuously infused for 3 h at a rate of 10 mg·kg -1·h -1, and the equal volume of normal saline was given instead in C and S groups. Rats were sacrificed at 24 h after LPS injection, blood samples from the abdominal aorta were collected for blood gas analysis, and the oxygenation index (OI), alveolar-arterial oxygen difference (A-aDO 2) and respiratory index (RI) were calculated. Then the chest was immediately opened, and the left lung tissues were then immediately removed to determine the levels of tumor necrosis factor-α (TNF-α), heme oxygenase-1 (HO-1) and reactive oxygen species (ROS) (by enzyme-linked immunosorbent assay). The right upper lung tissues were removed for microscopic examination of the alveolar structure and pulmonary edema with a light microscope. The right lower lung tissues were also removed to observe the vascular endothelial structure with a transmission electron microscope. Results:Compared with group C, the levels of A-aDO 2, RI, TNF-α, HO-1 and ROS were significantly increased, the PaO 2 and OI were decreased ( P<0.05), and no significant change was found in PaCO 2 in group S and group L ( P>0.05). Compared with group S, the PaO 2, OI and HO-1 were significantly increased, the levels of A-aDO 2, RI, TNF-α and ROS were decreased ( P<0.05), and no significant change was found in PaCO 2 levels in group L ( P>0.05). The pathological damages of the lung tissues were significantly attenuated in group L when compared with group S. Conclusions:Intravenous infusion of lidocaine can improve pulmonary gas exchange function during acute lung injury in septic rats.

Role of deubiquitinase OTUD1 in acute lung injury in septic mice: relationship with TAK1-MAPK signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of deubiquitinase OTUD1 in acute lung injury in septic mice and the relationship with transforming growth factor-beta activated kinase 1(TAK1)-mitogen-activated protein kinase (MAPK) signaling pathway.Methods:Twenty male wild-type (WT) and 20 OTUD1 gene knockout (KO) C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: wild-type+ sham operation group (WT-Sham group), wild-type+ sepsis group (WT-SEP group), OTUD1-KO+ sham operation group (KO-Sham group) and OTUD1-KO+ SEP group (KO-SEP group). The acute lung injury was induced by cecal ligation and perforation (CLP) in anesthetized septic mice. Mice were sacrificed at 24 h after operation, blood samples were collected from the abdominal aorta, and lung tissues were collected. Blood gas analysis was performed using the i-STAT blood gas analyzer, PaO 2 and FiO 2 were recorded, and the oxygenation index (OI) was calculated. The morphology of lung tissues was examined with a light microscope for evaluation of lung injury, and lung injury scores were calculated. The wet to dry lung weight (W/D) ratio was measured, and the activities of MPO were measured. The concentrations of TNF-α and IL-6 in plasma were detected by enzyme-linked immunosorbent assay, and the expression of OTUD1, phosphorylated TAK1 (p-TAK1), phosphorylated p38 (p-p38), phosphorylated c-Jun amino-terminal kinase (p-JNK) and phosphorylated extracellular signal-regulated kinase (p-ERK) was detected using Western blot. Results:Compared with WT-Sham group, the PaO 2 and OI were significantly decreased, the lung injury score, W/D ratio, MPO activity, and plasma TNF-α and IL-6 concentrations were increased, and the expression of OTUD1, p-TAK1, p-p38, p-JNK and p-ERK protein in lung tissues was up-regulated in WT-SEP group ( P<0.05). Compared with WT-SEP group, the PaO 2 and OI were significantly decreased, the lung injury score, W/D ratio, MPO activity, and plasma TNF-α and IL-6 concentrations were increased, and the expression of OTUD1, p-TAK1, p-p38, p-JNK and p-ERK protein in lung tissues was up-regulated in KO-SEP group ( P<0.05). Conclusions:OTUD1 is involved in the endogenous protective mechanism against acute lung injury in septic mice, which may be related to the inhibition of TAK1-MAPK signaling pathway activation and decreased inflammatory responses.

Effect of transcutaneous electrical acupoint stimulation on postoperative acute lung injury in pediatric patients undergoing living-related liver transplantation / 中华麻醉学杂志

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative acute lung injury (ALI) in the pediatric patients undergoing living-related liver transplantation.Methods:Sixty pediatric patients of either sex, aged 4-24 months, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association (NYHA) class Ⅰ or Ⅱ, with Child-Pugh B or C, scheduled to undergo elective left external lobe piggyback living-related liver transplantation, were divided into 2 groups ( n=30 each) using a computer-generated table of random numbers: control group (group C) and TEAS group (group T). In group T, bilateral Zusanli (ST36), Neiguan (PC6), and Feishu (BL13) acupoints were stimulated with disperse-dense waves at the initial intensity of 0.5 mA and frequency of 2/15 Hz, the current intensity was gradually increased until local slight muscle shaking appeared, and continuous stimulation lasted for 30 min at a 30-min interval (a cycle) until the end of operation. TEAS was performed for 30 min at the same time every day up to 1 week after surgery. Stimulus locations in group C were selected at 0.5 cm lateral to the acupoints, and the electrodes with inert medium were attached to the location, with no effective current output from acupuncture treatment instrument. The peak inspiratory pressure, plateau pressure, and pulmonary compliance were recorded before skin incision (T 0), at 30 min after portal vein occlusion (T 1), at 1 h after portal vein opening (T 2), at the end of operation (T 3), and the difference between peak inspiratory pressure and plateau pressure was calculated. Blood samples from the jugular vein were collected at T 0-3 to determine the levels of plasma club cell protein 16 (CC16), surfactant protein D (SP-D), soluble receptor for advanced glycation end products (sRAGE), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) by enzyme-linked immunosorbent assay. Blood samples from the radial artery were collected at T 0-3 for blood gas analysis, PaO 2 and A-aDO 2 were recorded, and oxygenation index (OI) and respiratory index (RI) were calculated. The indwelling time of postoperative tracheal tube and length of ICU stay were also recorded. The lung injury was assessed and scored using ultrasound at 48 h after surgery. The occurrence of ALI within 1 week after operation was also recorded. Results:Compared with baseline at T 0, OI was significantly decreased, RI was increased, and plasma IL-10 concentrations were increased at T 2, 3, and the plasma concentrations of TNF-α, CC16, sRAGE and SP-D were increased at T 1-3 in both groups ( P<0.05). Compared with group C, OI was significantly increased, RI was decreased, the plasma concentrations of sRAGE were decreased, and the plasma concentrations of IL-10 were increased at T 2, 3, and the concentrations of plasma TNF-α, CC16 and SP-D were decreased at T 1-3, the indwelling time of postoperative tracheal tube and length of ICU stay were shortened, the ultrasound score of lung injury was decreased ( P<0.05), and no significant change was found in the incidence of ALI in group T ( P>0.05). Conclusions:TEAS can alleviate ALI in the pediatric patients after living-related liver transplantation.

Risk factors for acute lung injury after pediatric living donor liver transplantation and the prediction value / 中华麻醉学杂志

Objective:To identify the risk factors for acute lung injury (ALI) after pediatric living donor liver transplantation (LDLT) and evaluate the predictive value.Methods:The pediatric patients (all diagnosed with congenital biliary atresia) who underwent parental liver transplantation in our center from January to December 2021 were selected. Perioperative data were obtained through the electronic medical record system, and the pediatric patients were divided into non-ALI group and ALI group according to whether ALI occurred or not at 1 week after surgery. The factors of which P values were less than 0.05 between groups would enter the multivariate logistic regression analysis to stratify the risk factors for ALI after pediatric LDLT, and the value of the risk factors in predicting intraoperative ALI was evaluated using the receiver operating characteristic curve. Results:A total of 140 pediatric patients were enrolled in the analysis, and the incidence of ALI was 30.7%. The results of the multivariate logistic regression analysis showed that preoperative pediatric end-stage liver disease score, preoperative serum NT-pro-BNP concentrations, intraoperative volume of fluid transfused, and duration of postreperfusion syndrome were independent risk factors for ALI after LDLT in pediatric patients ( P<0.05). The area under the receiver operating characteristic curve of the preoperative N-terminal pro-brain natriuretic peptide(NT-pro-BNP) concentration in predicting postoperative ALI was 0.737 ( P<0.001), with a cutoff value of 222.1 ng/L, sensitivity of 0.628, and specificity of 0.732. Conclusions:Preoperative pediatric end-stage liver disease score, serum NT-pro-BNP concentrations, intraoperative volume of fluid transfused, and duration of postreperfusion syndrome are independent risk factors for ALI after LDLT in pediatric patients; preoperative serum NT-pro-BNP concentrations can effectively predict the development of ALI after pediatric LDLT surgery.

Construction of a risk warning model for acute lung injury caused by Staphylococcus aureus infection / 中华传染病杂志

Objective:To investigate the risk factors of acute lung injury (ALI) caused by Staphylococcus aureus infection, and to construct a risk warning model. Methods:Patients with Staphylococcus aureus infection confirmed by sputum or blood culture admitted to the Affiliated Hospital of Jiangnan University from January 1, 2020 to May 10, 2022 were enrolled and divided into ALI group and non-ALI group. The age, smoking status, C-reactive protein (CRP), procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), albumin, oxygenation index and other clinical data were compared between the two groups. Univariate analysis was performed by using independent sample t test and chi-square test. Binary logistic regression analysis was used to screen the independent risk factors of ALI caused by Staphylococcus aureus infection, and a risk warning model was constructed. The receiver operator characteristic (ROC) curve was used to evaluate the predictive ability of the model. Results:There were 96 cases of Staphylococcus aureus infection, including 68 cases (70.8%) in ALI group, of which 41 cases (60.3%) were positive in sputum culture and 27 cases (39.7%) were positive in blood culture. Compared with the non-ALI group, the proportion of patients aged ≥60 years in ALI group was lower (58.8%(40/68) vs 64.3%(18/28)), the proportion of smoking was higher (58.8%(40/68) vs 35.7%(10/28)), and the differences were both statistically significant ( χ2=0.76 and 0.03, respectively, both P<0.05). The levels of CRP, PCT and NLR in the ALI group were all higher than those in non-ALI group, while oxygenation index and albumin level were both lower, and the differences were all statistically significant ( t=-5.28, -3.46, -9.87, 12.83 and 3.08, respectively, all P<0.05). Binary logistic regression analysis showed that CRP (odds ratio ( OR)=1.973, 95% confidence interval (95% CI) 0.956 to 2.989), PCT ( OR=3.734, 95% CI 1.014 to 13.746), NLR ( OR=1.152, 95% CI 1.058 to 2.254) and albumin ( OR=1.527, 95% CI 1.110 to 2.102) were independent risk factors for ALI caused by Staphylococcus aureus infection. The areas under the ROC curve of CRP, PCT, NLR, albumin and the risk warning model constructed from the combination of four risk factors were 0.69, 0.81, 0.83, 0.78 and 0.93, respectively. The sensitivities were 65.14%, 89.91%, 84.40%, 56.88% and 98.17%, respectively. The specificities were 62.37%, 60.22%, 65.59%, 80.64% and 93.55%, respectively. The accuracy of the effectiveness test of the risk warning model was 84.97%. Conclusions:CRP, PCT, NLR and albumin are the independent risk factors for ALI caused by Staphylococcus aureus infection. The risk warning model based on the above factors has a good early warning effect on ALI caused by Staphylococcus aureus infection.